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Publications Département Biologie des Génomes


  • I. Altinoglu, C. J. Merrifield, et Y. Yamaichi, « Single molecule super-resolution imaging of bacterial cell pole proteins with high-throughput quantitative analysis pipeline », Scientific Reports, vol. 9, nᵒ 1, p. 6680, avr. 2019.
    Résumé : Bacteria show sophisticated control of their cellular organization, and many bacteria deploy different polar landmark proteins to organize the cell pole. Super-resolution microscopy, such as Photo-Activated Localization Microscopy (PALM), provides the nanoscale localization of molecules and is crucial for better understanding of organization and dynamics in single-molecule. However, analytical tools are not fully available yet, in particular for bacterial cell biology. For example, quantitative and statistical analyses of subcellular localization with multiple cells from multiple fields of view are lacking. Furthermore, brightfield images are not sufficient to get accurate contours of small and low contrast bacterial cells, compared to subpixel presentation of target molecules. Here we describe a novel analytic tool for PALM which integrates precisely drawn cell outlines, of either inner membrane or periplasm, labelled by PALM-compatible fluorescent protein fusions, with molecule data for >10,000 molecules from >100 cells by fitting each cell into an oval arc. In the vibrioid bacterium Vibrio cholerae, the polar anchor HubP constitutes a big polar complex which includes multiple proteins involved in chemotaxis and the flagellum. With this pipeline, HubP is shown to be slightly skewed towards the inner curvature side of the cell, while its interaction partners showed rather loose polar localization.
    Mots-clés : BIOCELL, DBG, EQYY.

  • A. Briquet, R. Vong, J. - B. Roseau, E. Javelle, N. Cazes, F. Rivière, M. Aletti, M. - P. Otto, C. Ficko, S. Duron, M. Fabre, C. Pourcel, F. Simon, et C. Soler, « Clinical features of Mycobacterium canettii infection: a retrospective study of 20 cases among French soldiers and relatives », Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, févr. 2019.
    Résumé : Background: Mycobacterium canettii forms part of the Mycobacterium tuberculosis complex. M. canettii infections are mainly described in the Horn of Africa. The permanent presence of French soldiers in Djibouti raises the question of the risk of being infected with M. canettii. Our study aims to describe M. canettii infections among French military or their families between 1998 and 2015. Methods: This retrospective study relied on 3 sources of data: the reference centre for mycobacteria in the Biology Department at Percy military hospital in Paris, the French Military Center for Epidemiology and Public Health, and the scientific literature. After an exhaustive census of the strains, we studied the epidemiological data on 20 cases among French soldiers and their families. Results: 20 cases of M. canettii infections are reported, including 5 unpublished cases. Adenitis predominates (n = 15), especially in the cervico facial area and among children; one case was observed one month after dental care in Djibouti. The pulmonary forms were less frequent (n = 6) and 3 atypical forms are described. All patients had stayed in Djibouti. Conclusions: Cases of M. canettii infection among the French military consisted mainly of adenitis; disseminated forms were possible with immunodeficiency. Their evolution under specific treatments were comparable to tuberculosis. The presumed origin of the infection seemed to be environmental, possibly a water reservoir, and not due to human-to-human contagion.
    Mots-clés : DBG, LGBMB, MICROBIO, SSFA.

  • E. M. S. Brito, V. M. Romero-Núñez, C. A. Caretta, P. Bertin, J. C. Valerdi-Negreros, R. Guyoneaud, et M. Goñi-Urriza, « The bacterial diversity on steam vents from Paricutín and Sapichu volcanoes », Extremophiles: Life Under Extreme Conditions, févr. 2019.
    Résumé : Vapor steam vents are prevailing structures on geothermal sites in which local geochemical conditions allow the development of extremophilic microorganisms. We describe the structure of the prokaryotic community able to grow on the walls and rocks of such microecosystems in two terrestrial Mexican volcanoes: Paricutín (PI and PII samples) and its satellite Sapichu (S sample). The investigated samples showed similar diversity indices, with few dominant OTUs (abundance > 1%): 21, 16 and 23, respectively for PI, PII and S. However, each steam vent showed a particular community profile: PI was dominated by photosynthetic bacteria (Cyanobacteria and Chloroflexia class), PII by Actinobacteria and Proteobacteria, and S by Ktedonobacteria class, Acidobacteria and Cyanobacteria phyla. Concerning the predicted metabolic potential, we found a dominance of cellular pathways, especially the ones for energy generation with metabolisms for sulfur respiration, nitrogen fixation, methanogenesis, carbon fixation, photosynthesis, and metals, among others. We suggest a different maturity stage for the three studied fumaroles, from the youngest (PI) to the oldest (S and PII), also influenced by the temperature and other geochemical parameters. Furthermore, four anaerobic strains were isolated, belonging to Clostridia class (Clostridium sphenoides, C. swellfunanium and Anaerocolumna cellulosilytica) and to Bacilli class (Paenibacillus azoreducens).
    Mots-clés : Anaerobic bacteria, DBG, Extreme environment, GST, Microbial biodiversity, Predictive metagenomics profiling, Volcanic fumaroles.

  • D. Ciardo, A. Goldar, et K. Marheineke, « On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway », Genes, vol. 10, nᵒ 2, p. 94, janv. 2019.
    Résumé : DNA replication in eukaryotes is achieved by the activation of multiple replication origins which needs to be precisely coordinated in space and time. This spatio-temporal replication program is regulated by many factors to maintain genome stability, which is frequently threatened through stresses of exogenous or endogenous origin. Intra-S phase checkpoints monitor the integrity of DNA synthesis and are activated when replication forks are stalled. Their activation leads to the stabilization of forks, to the delay of the replication program by the inhibition of late firing origins, and the delay of G2/M phase entry. In some cell cycles during early development these mechanisms are less efficient in order to allow rapid cell divisions. In this article, we will review our current knowledge of how the intra-S phase checkpoint regulates the replication program in budding yeast and metazoan models, including early embryos with rapid S phases. We sum up current models on how the checkpoint can inhibit origin firing in some genomic regions, but allow dormant origin activation in other regions. Finally, we discuss how numerical and theoretical models can be used to connect the multiple different actors into a global process and to extract general rules.
    Mots-clés : ataxia-telangiectasia, ATR, Chk1, DBG, DNA replication, DYNREP, GTR, MBT.

  • I. Corcoles-Saez, J. - L. Ferat, M. Costanzo, C. M. Boone, et R. S. Cha, « Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase », Microbial Cell (Graz, Austria), vol. 6, nᵒ 6, p. 286-294, mai 2019.
    Résumé : Ribonucleotide reductase (RNR) is an essential holoenzyme required for de novo synthesis of dNTPs. The Saccharomyces cerevisiae genome encodes for two catalytic subunits, Rnr1 and Rnr3. While Rnr1 is required for DNA replication and DNA damage repair, the function(s) of Rnr3 is unknown. Here, we show that carbon source, an essential nutrient, impacts Rnr1 and Rnr3 abundance: Non-fermentable carbon sources or limiting concentrations of glucose down regulate Rnr1 and induce Rnr3 expression. Oppositely, abundant glucose induces Rnr1 expression and down regulates Rnr3. The carbon source dependent regulation of Rnr3 is mediated by Mec1, the budding yeast ATM/ATR checkpoint response kinase. Unexpectedly, this regulation is independent of all currently known components of the Mec1 DNA damage response network, including Rad53, Dun1, and Tel1, implicating a novel Mec1 signalling axis. rnr3Δ leads to growth defects under respiratory conditions and rescues temperature sensitivity conferred by the absence of Tom6, a component of the mitochondrial TOM (translocase of outer membrane) complex responsible for mitochondrial protein import. Together, these results unveil involvement of Rnr3 in mitochondrial functions and Mec1 in mediating the carbon source dependent regulation of Rnr3.
    Mots-clés : atr, autophagy, carbon source, cell-cycle, checkpoint, DBG, dna-damage response, dNTP, EMC2, gene, kinase, Mec1, Rnr1, Rnr3.

  • A. Demené, L. Legrand, J. Gouzy, R. Debuchy, G. Saint-Jean, O. Fabreguettes, et C. Dutech, « Whole-genome sequencing reveals recent and frequent genetic recombination between clonal lineages of Cryphonectria parasitica in western Europe », Fungal genetics and biology: FG & B, juin 2019.
    Résumé : Changes in the mode of reproduction are frequently observed in invasive fungal populations. The ascomycete Cryphonectria parasitica, which causes Chestnut Blight, was introduced to Europe from North America and Asia in the 20th century. Previous genotyping studies based on ten microsatellite markers have identified several clonal lineages which have spread throughout western Europe, suggesting that asexuality was the main reproductive mode of this species during colonization, although occasional sexual reproduction is not excluded. Based on the whole-genome sequences alignment of 46 C. parasitica isolates from France, North America and Asia, genealogy and population structure analyses mostly confirmed these lineages as clonal. However, one of these clonal lineages showed a signal of strong recombination, suggesting different strategies of reproduction in western Europe. Signatures of several recent recombination events within all the French clonal lineages studied here were also identified, indicating that gene flow is regular between these lineages. In addition, haplotype identification of seven French clonal lineages revealed that emergences of new clonal lineages during colonization were the result of hybridization between the main expanding clonal lineages and minor haplotypes non-sequenced in the present study. This whole-genome sequencing study underlines the importance of recombination events in the invasive success of these clonal populations, and suggests that sexual reproduction may be more frequent within and between the western European clonal lineages of C. parasitica than previously assumed using few genetic markers.
    Mots-clés : Bayesian inferences, clonal evolution, DBG, intra-haploid mating, MRP, recombination rates, whole genome sequencing.

  • T. Denecker, W. Durand, J. Maupetit, C. Hébert, J. - M. Camadro, P. Poulain, et G. Lelandais, « Pixel: a content management platform for quantitative omics data », PeerJ, vol. 7, p. e6623, 2019.
    Résumé : Background: In biology, high-throughput experimental technologies, also referred as "omics" technologies, are increasingly used in research laboratories. Several thousands of gene expression measurements can be obtained in a single experiment. Researchers are routinely facing the challenge to annotate, store, explore and mine all the biological information they have at their disposal. We present here the Pixel web application (Pixel Web App), an original content management platform to help people involved in a multi-omics biological project. Methods: The Pixel Web App is built with open source technologies and hosted on the collaborative development platform GitHub ( It is written in Python using the Django framework and stores all the data in a PostgreSQL database. It is developed in the open and licensed under the BSD 3-clause license. The Pixel Web App is also heavily tested with both unit and functional tests, a strong code coverage and continuous integration provided by CircleCI. To ease the development and the deployment of the Pixel Web App, Docker and Docker Compose are used to bundle the application as well as its dependencies. Results: The Pixel Web App offers researchers an intuitive way to annotate, store, explore and mine their multi-omics results. It can be installed on a personal computer or on a server to fit the needs of many users. In addition, anyone can enhance the application to better suit their needs, either by contributing directly on GitHub (encouraged) or by extending Pixel on their own. The Pixel Web App does not provide any computational programs to analyze the data. Still, it helps to rapidly explore and mine existing results and holds a strategic position in the management of research data.
    Mots-clés : BIM, candida-glabrata, Data cycle analyses, DBG, Omics, Open source, Pixel Web App.

  • A. Devigne, L. Meyer, C. B. de la Tour, N. Eugenie, S. Sommer, et P. Servant, « The absence of the RecN protein suppresses the cellular defects of Deinococcus radiodurans irradiated cells devoid of the PprA protein by Cheek tot limiting recombinational repair of DNA lesions », Dna Repair, vol. 73, p. 144-154, janv. 2019.
    Résumé : The Deinococcus radiodurans bacterium is one of the most radioresistant organisms known. It can repair hundreds of radiation-induced DNA double-strand breaks without loss of viability and reconstitute an intact genome through RecA-dependent and RecA-independent DNA repair pathways. Among the Deinococcus specific proteins required for radioresistance, the PprA protein was shown to play a major role for accurate chromosome segregation and cell division after completion of DNA repair. Here, we analyzed the cellular role of the deinococcal RecN protein belonging to the SMC family and, surprisingly, observed that the absence of the RecN protein suppressed the sensitivity of cells devoid of the PprA protein to gamma- and UV-irradiation and to treatment with MMC or DNA gyrase inhibitors. This suppression was not observed when Delta pprA cells were devoid of SMC or SbcC, two other proteins belonging to the SMC family. The absence of RecN also alleviated the DNA segregation defects displayed by Delta pprA cells recovering from y-irradiation. When exposed to 5 kGy gamma-irradiation, Delta pprA, Delta recN and Delta pprA Delta recN cells repaired their DNA with a delay of about one hour, as compared to the wild type cells. After irradiation, the absence of RecN reduced recombination between chromosomal and plasmid DNA, indicating that the deinococcal RecN protein is important for recombinational repair of DNA lesions. The transformation efficiency of genomic DNA was also reduced in the absence of the RecN protein. Here, we propose a model in which RecN, via its cohesin activity, might favor recombinational repair of DNA double strand breaks. This might increase, in irradiated cells, DNA constraints with PprA protein being required to resolve them via its ability to recruit DNA gyrase and to stimulate its decatenation activity.
    Mots-clés : chromosomes, complex, DBG, Deinococcus radiodurans, DNA segregation, DNA segregation, double-strand breaks, dynamics, Homologous recombination, identification, PprA, RBA, RecN, recruitment, replication, segregation, smc protein, structural maintenance.

  • E. Dubois, A. De Muyt, J. L. Soyer, K. Budin, M. Legras, T. Piolot, R. Debuchy, N. Kleckner, D. Zickler, et E. Espagne, « Building bridges to move recombination complexes », Proceedings of the National Academy of Sciences of the United States of America, mai 2019.
    Résumé : A central feature of meiosis is pairing of homologous chromosomes, which occurs in two stages: coalignment of axes followed by installation of the synaptonemal complex (SC). Concomitantly, recombination complexes reposition from on-axis association to the SC central region. We show here that, in the fungus Sordaria macrospora, this critical transition is mediated by robust interaxis bridges that contain an axis component (Spo76/Pds5), DNA, plus colocalizing Mer3/Msh4 recombination proteins and the Zip2-Zip4 mediator complex. Mer3-Msh4-Zip2-Zip4 colocalizing foci are first released from their tight axis association, dependent on the SC transverse-filament protein Sme4/Zip1, before moving to bridges and thus to a between-axis position. Ensuing shortening of bridges and accompanying juxtaposition of axes to 100 nm enables installation of SC central elements at sites of between-axis Mer3-Msh4-Zip2-Zip4 complexes. We show also that the Zip2-Zip4 complex has an intrinsic affinity for chromosome axes at early leptotene, where it localizes independently of recombination, but is dependent on Mer3. Then, later, Zip2-Zip4 has an intrinsic affinity for the SC central element, where it ultimately localizes to sites of crossover complexes at the end of pachytene. These and other findings suggest that the fundamental role of Zip2-Zip4 is to mediate the recombination/structure interface at all post-double-strand break stages. We propose that Zip2-Zip4 directly mediates a molecular handoff of Mer3-Msh4 complexes, from association with axis components to association with SC central components, at the bridge stage, and then directly mediates central region installation during SC nucleation.
    Mots-clés : chromosome structure, DBG, interaxis bridges, meiotic recombination, MRP, synaptonemal complex, Zip2-Zip4.

  • E. Durand, I. Gagnon-Arsenault, J. Hallin, I. Hatin, A. K. Dube, L. Nielly-Thibault, O. Namy, et C. R. Landry, « Turnover of ribosome-associated transcripts from de novo ORFs produces gene-like characteristics available for de novo gene emergence in wild yeast populations », Genome Research, vol. 29, nᵒ 6, p. 932-943, juin 2019.
    Résumé : Little is known about the rate of emergence of de novo genes, what their initial properties are, and how they spread in populations. We examined wild yeast populations (Saccharomyces paradoxus) to characterize the diversity and turnover of intergenic ORFs over short evolutionary timescales. We find that hundreds of intergenic ORFs show translation signatures similar to canonical genes, and we experimentally confirmed the translation of many of these ORFs in laboratory conditions using a reporter assay. Compared with canonical genes, intergenic ORFs have lower translation efficiency, which could imply a lack of optimization for translation or a mechanism to reduce their production cost. Translated intergenic ORFs also tend to have sequence properties that are generally close to those of random intergenic sequences. However, some of the very recent translated intergenic ORFs, which appeared <110 kya, already show gene-like characteristics, suggesting that the raw material for functional innovations could appear over short evolutionary timescales.
    Mots-clés : DBG, drosophila-yakuba, evolution, genome, GST, in-vivo, map, origin, sequences, translation.

  • C. Essoh, J. - P. Vernadet, G. Vergnaud, A. Coulibaly, A. Kakou-N'Douba, A. S. - P. N'Guetta, G. Resch, et C. Pourcel, « Complete Genome Sequences of Five Acinetobacter baumannii Phages from Abidjan, Côte d'Ivoire », Microbiology Resource Announcements, vol. 8, nᵒ 1, janv. 2019.
    Résumé : Five bacteriophages of Acinetobacter baumannii were isolated from sewage water in Abidjan, Côte d'Ivoire. Phages Aci01-1, Aci02-2, and Aci05 belong to an unclassified genus of the Myoviridae family, with double-stranded DNA (dsDNA) genomes, whereas Aci07 and Aci08 belong to the Fri1virus genus of the Podoviridae family of phages.
    Mots-clés : DBG, LGBMB, MICROBIO, SSFA.

  • A. Ferrandi, F. Gastoni, M. Pitaro, S. Tagliaferri, C. B. de la Tour, R. Alduina, S. Sommer, M. Fasano, P. Barbieri, M. Mancini, et I. M. Bonapace, « Deinococcus radiodurans' SRA-HNH domain containing protein Shp (Dr1533) is involved in faithful genome inheritance maintenance following DNA damage », Biochimica Et Biophysica Acta-General Subjects, vol. 1863, nᵒ 1, p. 118-129, janv. 2019.
    Résumé : Background: Deinococcus radiodurans R1 (DR) survives conditions of extreme desiccation, irradiation and exposure to genotoxic chemicals, due to efficient DNA breaks repair, also through Mn2+ protection of DNA repair enzymes. Methods: Possible annotated domains of the DR1533 locus protein (Shp) were searched by bioinformatic analysis. The gene was cloned and expressed as fusion protein. Band-shift assays of Shp or the SRA and HNH domains were performed on oligonucleotides, genomic DNA from E. coif and DR. slip knock-out mutant was generated by homologous recombination with a kanamycin resistance cassette. Results: DR1533 contains an N-terminal SRA domain and a C-terminal HNH motif (SRA-HNH Protein, Shp). Through its SRA domain, Shp binds double-strand oligonucleotides containing 5mC and 5hmC, but also unmethylated and mismatched cytosines in presence of Mn2+. Shp also binds to Escherichia coli dcm(+) genomic DNA, and to cytosine unmethylated DR and E. coli dcm(-) genomic DNAs, but only in presence of Mn2+. Under these binding conditions, Shp displays DNAse activity through its HNH domain. Shp KO enhanced > 100 fold the number of spontaneous mutants, whilst the treatment with DNA double strand break inducing agents enhanced up to 3-log the number of survivors. Conclusions: The SRA-HNH containing protein Shp binds to and cuts 5mC DNA, and unmethylated DNA in a Mn2+ dependent manner, and might be involved in faithful genome inheritance maintenance following DNA damage. General significance: Our results provide evidence for a potential role of DR Shp protein for genome integrity maintenance, following DNA double strand breaks induced by genotoxic agents.
    Mots-clés : cytosine, DBG, DNA cytosine-methylation, DNA damage, DR1533 locus, features, Genotoxic agents, manganese(ii), Mn2+, oxidation, perspective, RBA, recognition, repair, resistance, SRA domain, uhrf1.

  • A. Frapporti, C. Miró Pina, O. Arnaiz, D. Holoch, T. Kawaguchi, A. Humbert, E. Eleftheriou, B. Lombard, D. Loew, L. Sperling, K. Guitot, R. Margueron, et S. Duharcourt, « The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium », Nature Communications, vol. 10, nᵒ 1, p. 2710, juin 2019.
    Résumé : In animals and plants, the H3K9me3 and H3K27me3 chromatin silencing marks are deposited by different protein machineries. H3K9me3 is catalyzed by the SET-domain SU(VAR)3-9 enzymes, while H3K27me3 is catalyzed by the SET-domain Enhancer-of-zeste enzymes, which are the catalytic subunits of Polycomb Repressive Complex 2 (PRC2). Here, we show that the Enhancer-of-zeste-like protein Ezl1 from the unicellular eukaryote Paramecium tetraurelia, which exhibits significant sequence and structural similarities with human EZH2, catalyzes methylation of histone H3 in vitro and in vivo with an apparent specificity toward K9 and K27. We find that H3K9me3 and H3K27me3 co-occur at multiple families of transposable elements in an Ezl1-dependent manner. We demonstrate that loss of these histone marks results in global transcriptional hyperactivation of transposable elements with modest effects on protein-coding gene expression. Our study suggests that although often considered functionally distinct, H3K9me3 and H3K27me3 may share a common evolutionary history as well as a common ancestral role in silencing transposable elements.
    Mots-clés : chromatin, complex, DBG, genes, heterochromatin formation, histone methyltransferase activity, mechanisms, MICMAC, pluripotent, specificity, states, structural basis.

  • A. Frapporti, C. Miró Pina, O. Arnaiz, D. Holoch, T. Kawaguchi, A. Humbert, E. Eleftheriou, B. Lombard, D. Loew, L. Sperling, K. Guitot, R. Margueron, et S. Duharcourt, « The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium », Nature Communications, vol. 10, nᵒ 1, p. 2710, 2019.
    Résumé : In animals and plants, the H3K9me3 and H3K27me3 chromatin silencing marks are deposited by different protein machineries. H3K9me3 is catalyzed by the SET-domain SU(VAR)3-9 enzymes, while H3K27me3 is catalyzed by the SET-domain Enhancer-of-zeste enzymes, which are the catalytic subunits of Polycomb Repressive Complex 2 (PRC2). Here, we show that the Enhancer-of-zeste-like protein Ezl1 from the unicellular eukaryote Paramecium tetraurelia, which exhibits significant sequence and structural similarities with human EZH2, catalyzes methylation of histone H3 in vitro and in vivo with an apparent specificity toward K9 and K27. We find that H3K9me3 and H3K27me3 co-occur at multiple families of transposable elements in an Ezl1-dependent manner. We demonstrate that loss of these histone marks results in global transcriptional hyperactivation of transposable elements with modest effects on protein-coding gene expression. Our study suggests that although often considered functionally distinct, H3K9me3 and H3K27me3 may share a common evolutionary history as well as a common ancestral role in silencing transposable elements.
    Mots-clés : DBG, DNA Methylation, DNA Transposable Elements, Gene Silencing, Histones, MICMAC, Paramecium tetraurelia, Polycomb Repressive Complex 2, Protein Processing, Post-Translational, Transcriptional Activation.
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  • E. Galli, J. - L. Ferat, J. - M. Desfontaines, M. - E. Val, O. Skovgaard, F. - X. Barre, et C. Possoz, « Replication termination without a replication fork trap », Scientific Reports, vol. 9, nᵒ 1, p. 8315, juin 2019.
    Résumé : Bacterial chromosomes harbour a unique origin of bidirectional replication, oriC. They are almost always circular, with replication terminating in a region diametrically opposite to oriC, the terminus. The oriC-terminus organisation is reflected by the orientation of the genes and by the disposition of DNA-binding protein motifs implicated in the coordination of chromosome replication and segregation with cell division. Correspondingly, the E. coli and B. subtilis model bacteria possess a replication fork trap system, Tus/ter and RTP/ter, respectively, which enforces replication termination in the terminus region. Here, we show that tus and rtp are restricted to four clades of bacteria, suggesting that tus was recently domesticated from a plasmid gene. We further demonstrate that there is no replication fork system in Vibrio cholerae, a bacterium closely related to E. coli. Marker frequency analysis showed that replication forks originating from ectopic origins were not blocked in the terminus region of either of the two V. cholerae chromosomes, but progressed normally until they encountered an opposite fork. As expected, termination synchrony of the two chromosomes is disrupted by these ectopic origins. Finally, we show that premature completion of the primary chromosome replication did not modify the choreography of segregation of its terminus region.
    Mots-clés : binding, cell-division, DBG, dna-replication, EMC2, escherichia-coli-chromosome, ftsk, protein, segregation, terminus region, tus, vibrio-cholerae.

  • A. Georges, D. Gopaul, C. Denby Wilkes, N. Giordanengo Aiach, E. Novikova, M. - B. Barrault, O. Alibert, et J. Soutourina, « Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin », Nucleic Acids Research, juill. 2019.
    Résumé : Transcription and maintenance of genome integrity are fundamental cellular functions. Deregulation of transcription and defects in DNA repair lead to serious pathologies. The Mediator complex links RNA polymerase (Pol) II transcription and nucleotide excision repair via Rad2/XPG endonuclease. However, the functional interplay between Rad2/XPG, Mediator and Pol II remains to be determined. In this study, we investigated their functional dynamics using genomic and genetic approaches. In a mutant affected in Pol II phosphorylation leading to Mediator stabilization on core promoters, Rad2 genome-wide occupancy shifts towards core promoters following that of Mediator, but decreases on transcribed regions together with Pol II. Specific Mediator mutations increase UV sensitivity, reduce Rad2 recruitment to transcribed regions, lead to uncoupling of Rad2, Mediator and Pol II and to colethality with deletion of Rpb9 Pol II subunit involved in transcription-coupled repair. We provide new insights into the functional interplay between Rad2, Mediator and Pol II and propose that dynamic interactions with Mediator and Pol II are involved in Rad2 loading to the chromatin. Our work contributes to the understanding of the complex link between transcription and DNA repair machineries, dysfunction of which leads to severe diseases.
    Mots-clés : DBG, GTR.

  • E. Godat, J. - C. Preiser, J. - C. Aude, et P. Kalfon, « Dynamic properties of glucose complexity during the course of critical illness: a pilot study », Journal of Clinical Monitoring and Computing, mars 2019.
    Résumé : Methods to control the blood glucose (BG) levels of patients in intensive care units (ICU) improve the outcomes. The development of continuous BG levels monitoring devices has also permitted to optimize these processes. Recently it was shown that a complexity loss of the BG signal is linked to poor clinical outcomes. Thus, it becomes essential to decipher this relation to design efficient BG level control methods. In previous studies the BG signal complexity was calculated as a single index for the whole ICU stay. Although, these approaches did not grasp the potential variability of the BG signal complexity. Therefore, we setup this pilot study using a continuous monitoring of central venous BG levels in ten critically ill patients (EIRUS platform, Maquet Critical CARE AB, Solna, Sweden). Data were processed and the complexity was assessed by the detrended fluctuation analysis and multiscale entropy (MSE) methods. Finally, recordings were split into 24 h overlapping intervals and a MSE analysis was applied to each of them. The MSE analysis on time intervals revealed an entropy variation and allowed periodic BG signal complexity assessments. To highlight differences of MSE between each time interval we calculated the MSE complexity index defined as the area under the curve. This new approach could pave the way to future studies exploring new strategies aimed at restoring blood glucose complexity during the ICU stay.
    Mots-clés : BIM, Continuous glucose monitoring, Critically ill patients, DBG, Glucose control, Multiscale entropy, Signal complexity.

  • J. Godau, L. P. Ferretti, A. Trenner, E. Dubois, C. von Aesch, A. Marmignon, L. Simon, A. Kapusta, R. Guérois, M. Bétermier, et A. A. Sartori, « Identification of a miniature Sae2/Ctp1/CtIP ortholog from Paramecium tetraurelia required for sexual reproduction and DNA double-strand break repair », DNA repair, vol. 77, p. 96-108, mars 2019.
    Résumé : DNA double-strand breaks (DSBs) induced by genotoxic agents can cause cell death or contribute to chromosomal instability, a major driving force of cancer. By contrast, Spo11-dependent DSBs formed during meiosis are aimed at generating genetic diversity. In eukaryotes, CtIP and the Mre11 nuclease complex are essential for accurate processing and repair of both unscheduled and programmed DSBs by homologous recombination (HR). Here, we applied bioinformatics and genetic analysis to identify Paramecium tetraurelia CtIP (PtCtIP), the smallest known Sae2/Ctp1/CtIP ortholog, as a key factor for the completion of meiosis and the recovery of viable sexual progeny. Using in vitro assays, we find that purified recombinant PtCtIP preferentially binds to double-stranded DNA substrates but does not contain intrinsic nuclease activity. Moreover, mutation of the evolutionarily conserved C-terminal 'RHR' motif abrogates DNA binding of PtCtIP but not its ability to functionally interact with Mre11. Translating our findings into mammalian cells, we provide evidence that disruption of the 'RHR' motif abrogates accumulation of human CtIP at sites of DSBs. Consequently, cells expressing the DNA binding mutant CtIPR837A/R839A are defective in DSB resection and HR. Collectively, our work highlights minimal structural requirements for CtIP protein family members to facilitate the processing of DSBs, thereby maintaining genome stability as well as enabling sexual reproduction.
    Mots-clés : AMIG, B3S, CtIP, ctp1, damage response, DBG, DNA double-strand breaks, DNA end resection, end-resection, endonuclease, gene, Homologous recombination, human ctip, Meiosis, MICMAC, mre11 complex, Paramecium tetraurelia, protein, rad32(mre11) nuclease, sae2.

  • A. Gorlas, R. Catchpole, E. Marguet, et P. Forterre, « Increase of positive supercoiling in a hyperthermophilic archaeon after UV irradiation », Extremophiles, vol. 23, nᵒ 1, p. 141-149, janv. 2019.
    Résumé : Diverse DNA repair mechanisms are essential to all living organisms. Some of the most widespread repair systems allow recovery of genome integrity in the face of UV radiation. Here, we show that the hyperthermophilic archaeon Thermococcus nautili possesses a remarkable ability to recovery from extreme chromosomal damage. Immediately following UV irradiation, chromosomal DNA of T. nautili is fragmented beyond recognition. However, the extensive UV-induced double-stranded breaks (DSB) are repaired over the course of several hours, allowing restoration of growth. DSBs also disrupted plasmid DNA in this species. Similar to the chromosome, plasmid integrity was restored during an outgrowth period. Intriguingly, the topology of recovered pTN1 plasmids differed from control strain by being more positively supercoiled. As reverse gyrase (RG) is the only enzyme capable of inducing positive supercoiling, our results suggest the activation of RG activity by UV-induced stress. We suggest simple UV stress could be used to study archaeal DNA repair and responses to DSB.
    Mots-clés : ARCHEE, DBG, Double-strand breaks, MICROBIO, Plasmid, RBA, Topology, UV irradiation.

  • M. V. C. Greenberg, A. Teissandier, M. Walter, D. Noordermeer, et D. Bourc'his, « Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency », eLife, vol. 8, avr. 2019.
    Résumé : During early mammalian development, the chromatin landscape undergoes profound transitions. The Zdbf2 gene-involved in growth control-provides a valuable model to study this window: upon exit from naïve pluripotency and prior to tissue differentiation, it undergoes a switch from a distal to a proximal promoter usage, accompanied by a switch from polycomb to DNA methylation occupancy. Using an embryonic stem cell (ESC) system to mimic this period, we show here that four enhancers contribute to the Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. In ESCs, the locus is partitioned to facilitate enhancer contacts with the distal Zdbf2 promoter. Relieving the partition enhances proximal Zdbf2 promoter activity, as observed during differentiation or with genetic mutants. Importantly, we show that 3D regulation occurs upstream of the polycomb and DNA methylation pathways. Our study reveals the importance of multi-layered regulatory frameworks to ensure proper spatio-temporal activation of developmentally important genes.
    Mots-clés : CHRODY, chromosomes, DBG, differentiation, DNA methylation, enhancers, epigenetics, gene expression, genetics, genomics, mouse, polycomb, stem cells.

  • M. A. Hanson, A. Dostálová, C. Ceroni, M. Poidevin, S. Kondo, et B. Lemaitre, « Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach », eLife, vol. 8, févr. 2019.
    Résumé : Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete all known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.
    Mots-clés : AMP, D. melanogaster, DBG, Diptericin, Drosocin, EQYY, Imd, immunology, inflammation, PF, systemic immunity, Toll.

  • D. Knierim, Q. Barrière, I. Grigoras, S. Winter, H. - J. Vetten, M. Schwinghamer, J. Thomas, P. Chu, B. Gronenborn, et T. Timchenko, « Subterranean Clover Stunt Virus Revisited: Detection of Two Missing Genome Components », Viruses, vol. 11, nᵒ 2, p. 138, févr. 2019.
    Résumé : Subterranean clover stunt virus (SCSV) is a type species of the genus Nanovirus in the family Nanoviridae. It was the first single-stranded DNA plant virus with a multipartite genome, of which genomic DNA sequences had been determined. All nanoviruses have eight genome components except SCSV, for which homologs of two genome components present in all other nanovirus genomes, DNA-U2 and DNA-U4, were lacking. We analysed archived and more recent samples from SCSV-infected legume plants to verify its genome composition and found the missing genome components. These results indicated that SCSV also has eight genome components and is a typical member of the genus Nanovirus.
    Mots-clés : circular ssdna components, DBG, dna, dwarf virus, high-throughput sequencing, high-throughput sequencing, identification, MICROBIO, nanovirus, nanovirus-alphasatellite complex, necrotic yellows virus, PBI, pea, PROMTI, proteins, recombination, replication, rolling circle replication, virus evolution.

  • L. Latino, C. Midoux, G. Vergnaud, et C. Pourcel, « Investigation of Pseudomonas aeruginosa strain PcyII-10 variants resisting infection by N4-like phage Ab09 in search for genes involved in phage adsorption », PloS One, vol. 14, nᵒ 4, p. e0215456, 2019.
    Résumé : Bacteria and their bacteriophages coexist and coevolve for the benefit of both in a mutualistic association. Multiple mechanisms are used by bacteria to resist phages in a trade-off between survival and maintenance of fitness. In vitro studies allow inquiring into the fate of virus and host in different conditions aimed at mimicking natural environment. We analyse here the mutations emerging in a clinical Pseudomonas aeruginosa strain in response to infection by Ab09, a N4-like lytic podovirus and describe a variety of chromosomal deletions and mutations conferring resistance. Some deletions result from illegitimate recombination taking place during long-term maintenance of the phage genome. Phage variants with mutations in a tail fiber gene are selected during pseudolysogeny with the capacity to infect resistant cells and produce large plaques. These results highlight the complex host/phage association and suggest that phage Ab09 promotes bacterial chromosome rearrangements. Finally this study points to the possible role of two bacterial genes in Ab09 phage adhesion to the cell, rpsB encoding protein S2 of the 30S ribosomal subunit and ORF1587 encoding a Wzy-like membrane protein involved in LPS biosynthesis.
    Mots-clés : bacteriophages, chromosomal deletion, comparative genomics, DBG, escherichia-coli, fine-structure, mechanisms, o-antigen, pseudolysogeny, replication, resistance, SSFA.

  • L. Latino, D. Patin, D. Cherier, T. Touze, C. Pourcel, H. Barreteau, et D. Mengin-Lecreulx, « Impact of FiuA Outer Membrane Receptor Polymorphism on the Resistance of Pseudomonas aeruginosa toward Peptidoglycan Lipid II-Targeting PaeM Pyocins », Journal of Bacteriology, vol. 201, nᵒ 13, p. e00164, juill. 2019.
    Résumé : Certain Pseudomonas aeruginosa strains produce a homolog of colicin M, namely, PaeM, that specifically inhibits peptidoglycan biosynthesis of susceptible P. aeruginosa strains by hydrolyzing the lipid II intermediate precursor. Two variants of this pyocin were identified whose sequences mainly differed in the N-terminal protein moiety, i.e., the region involved in the binding to the FiuA outer membrane receptor and translocation into the periplasm. The antibacterial activity of these two variants, PaeM1 and PaeM2, was tested against various P. aeruginosa strains comprising reference strains PAO1 and PA14, PaeM-producing strains, and 60 clinical isolates. Seven of these strains, including PAO1, were susceptible to only one variant (2 to PaeM1 and 5 to PaeM2), and 11 were affected by both. The remaining strains, including PA14 and four PaeM1 producers, were resistant to both variants. The differences in the antibacterial spectra of the two PaeM homologs prompted us to investigate the molecular determinants allowing their internalization into P. aeruginosa cells, taking the PAO1 strain that is susceptible to PaeM2 but resistant to PaeM1 as the indicator strain. Heterologous expression of fiuA gene orthologs from different strains into PAO1, site-directed mutagenesis experiments, and construction of PaeM chimeric proteins provided evidence that the cell susceptibility and discrimination differences between the PaeM variants resulted from a polymorphism of both the pyocin and the outer membrane receptor FiuA. Moreover, we found that a third component, TonB1, a protein involved in iron transport in P. aeruginosa, working together with FiuA and the ExbB/ExbD complex, was directly implicated in this discrimination. IMPORTANCE Bacterial antibiotic resistance constitutes a threat to human health, imposing the need for identification of new targets and development of new strategies to fight multiresistant pathogens. Bacteriocins and other weapons that bacteria have themselves developed to kill competitors are therefore of great interest and a valuable source of inspiration for us. Attention was paid here to two variants of a colicin M homolog (PaeM) produced by certain strains of P. aeruginosa that inhibit the growth of their congeners by blocking cell wall peptidoglycan synthesis. Molecular determinants allowing recognition of these pyocins by the outer membrane receptor FiuA were identified, and a receptor polymorphism affecting the susceptibility of P. aeruginosa clinical strains was highlighted, providing new insights into the potential use of these pyocins as an alternative to antibiotics.
    Mots-clés : acquisition, bacteriocins, cell wall, colicin M, colicin-m, crystal-structure, DBG, emergence, ENVBAC, escherichia-coli, FiuA, lipid II, locus variable-number, mechanism, MICROBIO, PaeM pyocins, peptidoglycan, protein, Pseudomonas aeruginosa, receptor structure-function, sequence, SSFA, TonB, tonb gene.

  • B. Le Cam, D. Sargent, J. Gouzy, J. Amselem, M. - N. Bellanger, O. Bouchez, S. Brown, V. Caffier, M. De Gracia Coquerel, R. Debuchy, L. Duvaux, T. Payen, M. Sannier, J. Shiller, J. Collemare, et C. Lemaire, « Population Genome Sequencing of the Scab Fungal Species Venturia inaequalis, Venturiapirina, Venturia aucupariae and Venturia asperata », G3 (Bethesda, Md.), juin 2019.
    Résumé : The Venturia genus comprises fungal species that are pathogens on Rosaceae host plants, including V. inaequalis and V. asperata on apple, V. aucupariae on sorbus and V. pirina on pear. Although the genetic structure of V. inaequalis populations has been investigated in detail, genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87 Venturia strains that represent each species and each population within V. inaequalis We present a PacBio genome assembly for the V. inaequalis EU-B04 reference isolate. The size of selected genomes was determined by flow cytometry, and varied from 45 to 93 Mb. Genome assemblies of V. inaequalis and V. aucupariae contain a high content of transposable elements (TEs), most of which belong to the Gypsy or Copia LTR superfamilies and have been inactivated by Repeat-Induced Point mutations. The reference assembly of V. inaequalis presents a mosaic structure of GC-equilibrated regions that mainly contain predicted genes and AT-rich regions, mainly composed of TEs. Six pairs of strains were identified as clones. Single-Nucleotide Polymorphism (SNP) analysis between these clones revealed a high number of SNPs that are mostly located in AT-rich regions due to misalignments and allowed determining a false discovery rate. The availability of these genome sequences is expected to stimulate genetics and population genomics research of Venturia pathogens. Especially, it will help understanding the evolutionary history of Venturia species that are pathogenic on different hosts, a history that has probably been substantially influenced by TEs.
    Mots-clés : apple, apple scab, DBG, effectors, formae specialis, Fusicladium, MRP, pear, transposable elements, Venturia.

  • M. B. Ledwaba, C. Gomo, K. E. Lekota, P. Le Flèche, A. Hassim, G. Vergnaud, et H. van Heerden, « Molecular characterization of Brucella species from Zimbabwe », PLoS neglected tropical diseases, vol. 13, nᵒ 5, p. e0007311, mai 2019.
    Résumé : Brucella abortus and B. melitensis have been reported in several studies in animals in Zimbabwe but the extent of the disease remains poorly known. Thus, characterizing the circulating strains is a critical first step in understanding brucellosis in the country. In this study we used an array of molecular assays including AMOS-PCR, Bruce-ladder, multiple locus variable number tandem repeats analysis (MLVA) and single nucleotide polymorphisms from whole genome sequencing (WGS-SNP) to characterize Brucella isolates to the species, biovar, and individual strain level. Sixteen Brucella strains isolated in Zimbabwe at the Central Veterinary laboratory from various hosts were characterized using all or some of these assays. The strains were identified as B. ovis, B. abortus, B. canis and B. suis, with B. canis being the first report of this species in Zimbabwe. Zimbabwean strains identified as B. suis and B. abortus were further characterized with whole genome sequencing and were closely related to reference strains 1330 and 86/8/59, respectively. We demonstrate the range of different tests that can be performed from simple assays that can be run in laboratories lacking sophisticated instrumentation to whole genome analyses that currently require substantial expertise and infrastructure often not available in the developing world.
    Mots-clés : abortus, DBG, differentiation, genome sequence, identification, ladder, melitensis, multiplex pcr assay, reveals, SSFA, strains, suis.

  • C. Loiseau, D. Brites, I. Moser, F. Coll, C. Pourcel, S. Robbe-Austerman, V. Escuyer, K. A. Musser, S. J. Peacock, S. Feuerriegel, T. A. Kohl, S. Niemann, S. Gagneux, et C. U. Koser, « Revised Interpretation of the Hain Lifescience GenoType MTBC To Differentiate Mycobacterium canettii and Members of the Mycobacterium tuberculosis Complex », Antimicrobial Agents and Chemotherapy, vol. 63, nᵒ 6, p. e00159-19, juin 2019.
    Résumé : Using 894 phylogenetically diverse genomes of the Mycobacterium tuberculosis complex (MTBC), we simulated in silico the ability of the Hain Lifescience GenoType MTBC assay to differentiate the causative agents of tuberculosis. Here, we propose a revised interpretation of this assay to reflect its strengths (e.g., it can distinguish some strains of Mycobacterium canettii and variants of Mycobacterium bovis that are not intrinsically resistant to pyrazinamide) and limitations (e.g., Mycobacterium orygis cannot be differentiated from Mycobacterium africanum).
    Mots-clés : assay, DBG, genotyping, intrinsic antibiotic resistance, Mycobacterium tuberculosis, orygis, polymorphisms, pyrazinamide, SSFA.

  • M. - C. Maurel, F. Leclerc, J. Vergne, et G. Zaccai, « RNA Back and Forth: Looking through Ribozyme and Viroid Motifs », Viruses, vol. 11, nᵒ 3, p. 283, mars 2019.
    Résumé : Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the widespread occurrence of HHRs in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitous features of life. Those are the structural and functional versatility of small RNAs, ribozymes, and viroids, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.
    Mots-clés : catalytic-activity, circular rnas, crystal-structure, DBG, evolution, hammerhead ribozymes, in-vitro, origins of life, replication, ribozyme, RNA world, rolling-circles, self-cleavage, SSFA, viroid, virus.

  • A. H. Millar, J. L. Heazlewood, C. Giglione, M. J. Holdsworth, A. Bachmair, et W. X. Schulze, « The Scope, Functions, and Dynamics of Posttranslational Protein Modifications », Annual Review of Plant Biology, févr. 2019.
    Résumé : Assessing posttranslational modification (PTM) patterns within protein molecules and reading their functional implications present grand challenges for plant biology. We combine four perspectives on PTMs and their roles by considering five classes of PTMs as examples of the broader context of PTMs. These include modifications of the N terminus, glycosylation, phosphorylation, oxidation, and N-terminal and protein modifiers linked to protein degradation. We consider the spatial distribution of PTMs, the subcellular distribution of modifying enzymes, and their targets throughout the cell, and we outline the complexity of compartmentation in understanding of PTM function. We also consider PTMs temporally in the context of the lifetime of a protein molecule and the need for different PTMs for assembly, localization, function, and degradation. Finally, we consider the combined action of PTMs on the same proteins, their interactions, and the challenge ahead of integrating PTMs into an understanding of protein function in plants. Expected final online publication date for the Annual Review of Plant Biology Volume 70 is April 29, 2019. Please see for revised estimates.
    Mots-clés : DBG, PROMTI.

  • A. Morillon et D. Gautheret, « Bridging the gap between reference and real transcriptomes », Genome Biology, vol. 20, nᵒ 1, p. 112, juin 2019.
    Résumé : Genetic, transcriptional, and post-transcriptional variations shape the transcriptome of individual cells, rendering establishing an exhaustive set of reference RNAs a complicated matter. Current reference transcriptomes, which are based on carefully curated transcripts, are lagging behind the extensive RNA variation revealed by massively parallel sequencing. Much may be missed by ignoring this unreferenced RNA diversity. There is plentiful evidence for non-reference transcripts with important phenotypic effects. Although reference transcriptomes are inestimable for gene expression analysis, they may turn limiting in important medical applications. We discuss computational strategies for retrieving hidden transcript diversity.
    Mots-clés : DBG, SSFA.

  • I. Nekrasova, V. Nikitashina, S. Bhullar, O. Arnaiz, D. P. Singh, E. Meyer, et A. Potekhin, « Loss of a Fragile Chromosome Region leads to the Screwy Phenotype in Paramecium tetraurelia », Genes, vol. 10, nᵒ 7, juill. 2019.
    Résumé : A conspicuous cell-shape phenotype known as "screwy" was reported to result from mutations at two or three uncharacterized loci in the ciliate Paramecium tetraurelia. Here, we describe a new screwy mutation, Spinning Top, which appeared spontaneously in the cross of an unrelated mutant with reference strain 51. The macronuclear (MAC) genome of the Spinning Top mutant is shown to lack a ~28.5-kb segment containing 18 genes at the end of one chromosome, which appears to result from a collinear deletion in the micronuclear (MIC) genome. We tested several candidate genes from the deleted locus by dsRNA-induced silencing in wild-type cells, and identified a single gene responsible for the phenotype. This gene, named Spade, encodes a 566-aa glutamine-rich protein with a C2HC zinc finger. Its silencing leads to a fast phenotype switch during vegetative growth, but cells recover a wild-type phenotype only 5-6 divisions after silencing is stopped. We analyzed 5 independently-obtained mutant alleles of the Sc1 locus, and concluded that all of them also lack the Spade gene and a number of neighboring genes in the MAC and MIC genomes. Mapping of the MAC deletion breakpoints revealed two different positions among the 5 alleles, both of which differ from the Spinning Top breakpoint. These results suggest that this MIC chromosome region is intrinsically unstable in strain 51.
    Mots-clés : chromosome fragile sites, cortical inheritance, DBG, epimutation, maternal inheritance, MICMAC, micronuclear deletion, Paramecium, trichocysts.
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  • I. Nekrasova, V. Nikitashina, S. Bhullar, O. Arnaiz, D. P. Singh, E. Meyer, et A. Potekhin, « Loss of a Fragile Chromosome Region leads to the Screwy Phenotype in Paramecium tetraurelia », Genes, vol. 10, nᵒ 7, juill. 2019.
    Résumé : A conspicuous cell-shape phenotype known as "screwy" was reported to result from mutations at two or three uncharacterized loci in the ciliate Paramecium tetraurelia. Here, we describe a new screwy mutation, Spinning Top, which appeared spontaneously in the cross of an unrelated mutant with reference strain 51. The macronuclear (MAC) genome of the Spinning Top mutant is shown to lack a ~28.5-kb segment containing 18 genes at the end of one chromosome, which appears to result from a collinear deletion in the micronuclear (MIC) genome. We tested several candidate genes from the deleted locus by dsRNA-induced silencing in wild-type cells, and identified a single gene responsible for the phenotype. This gene, named Spade, encodes a 566-aa glutamine-rich protein with a C2HC zinc finger. Its silencing leads to a fast phenotype switch during vegetative growth, but cells recover a wild-type phenotype only 5-6 divisions after silencing is stopped. We analyzed 5 independently-obtained mutant alleles of the Sc1 locus, and concluded that all of them also lack the Spade gene and a number of neighboring genes in the MAC and MIC genomes. Mapping of the MAC deletion breakpoints revealed two different positions among the 5 alleles, both of which differ from the Spinning Top breakpoint. These results suggest that this MIC chromosome region is intrinsically unstable in strain 51.
    Mots-clés : chromosome fragile sites, cortical inheritance, DBG, epimutation, maternal inheritance, MICMAC, micronuclear deletion, Paramecium, trichocysts.

  • T. B. Nesterova, G. Wei, H. Coker, G. Pintacuda, J. S. Bowness, T. Zhang, M. Almeida, B. Bloechl, B. Moindrot, E. J. Carter, I. Alvarez Rodrigo, Q. Pan, Y. Bi, C. - X. Song, et N. Brockdorff, « Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation », Nature Communications, vol. 10, nᵒ 1, p. 3129, juill. 2019.
    Résumé : Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in mouse embryonic stem cell-based models. Using a machine learning approach we identify distance to the Xist locus and prior gene expression levels as key determinants of silencing efficiency. We go on to show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/m6A-methyltransferase complex make only minor contributions to gene silencing. Together our results provide a comprehensive model for Xist-mediated chromosome silencing.
    Mots-clés : CHRODY, DBG.
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  • N. Paleiron, C. Soler, M. O. Hassan, D. Andriamanantena, R. Vong, C. Pourcel, et J. - B. Roseau, « First description of Mycobacterium tuberculosis and M. canettii concomitant infection: report of two cases », International Journal of Tuberculosis and Lung Disease, vol. 23, nᵒ 2, p. 232-+, janv. 2019.
    Résumé : <h2>SUMMARY</h2>We report the first two cases of tuberculous coinfection with Mycobacterium tuberculosis and M. canettii. Both patients were young Djiboutian females with pulmonary tuberculosis (TB). One had a miliary pattern with concomitant human immunodeficiency virus infection. Both recovered completely with a standard four-drug anti-tuberculosis treatment regimen. Due to the different natural reservoirs and routes of infection of these two strains, our study supports the common belief that multiple strains of infection in TB are related to superinfection rather than concomitant infection.
    Mots-clés : CHERDIR, coinfection, DBG, Mycobacterium canettii, SSFA, tuberculosis.

  • A. Petitalot, E. Dardillac, E. Jacquet, N. Nhiri, J. Guirouilh-Barbat, P. Julien, I. Bouazzaoui, D. Bonte, J. Feunteun, J. A. Schnell, P. Lafitte, J. - C. Aude, C. Nogues, E. Rouleau, R. Lidereau, B. S. Lopez, S. Zinn-Justin, S. M. Caputo, F. Bonnet, N. Jones, V. Bubien, M. Longy, N. Sevenet, S. Krieger, L. Casters, D. Vaur, N. Uhrhammer, Y. J. Bignon, S. Lizard, A. Dumont, F. Revillion, M. Leone, N. Boutry-Kryza, O. Sinilnikova, A. Remenieras, V. Bourdon, T. Noguchi, H. Sobol, P. - O. Harmand, P. Vilquin, P. Pujol, P. Jonveaux, M. Bronner, J. Sokolowska, C. Delnatte, V. Guibert, C. Garrec, S. Bezieau, F. Soubrier, E. Guillerm, F. Coulet, C. Lefol, V. Caux-Moncoutier, L. Golmard, C. Houdayer, D. Stoppa-Lyonnet, C. Delvincoun, O. Beaudoux, D. Muller, C. Toulas, M. Guillaud-Bataille, et B. Bressac-De Paillerets, « Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk », Molecular Cancer Research, vol. 17, nᵒ 1, p. 54-69, janv. 2019.
    Résumé : BRCA1 mutations have been identified that increase the risk of developing hereditary breast and ovarian cancers. Genetic screening is now offered to patients with a family history of cancer, to adapt their treatment and the management of their relatives. However, a large number of BRCA1 variants of uncertain significance (VUS) are detected. To better understand the significance of these variants, a high-throughput structural and functional analysis was performed on a large set of BRCA1 VUS. Information on both cellular localization and homology-directed DNA repair (HR) capacity was obtained for 78 BRCT missense variants in the UMD-BRCA1 database and measurement of the structural stability and phosphopeptide-binding capacities was performed for 42 mutated BRCT domains. This extensive and systematic analysis revealed that most characterized causal variants affect BRCT-domain solubility in bacteria and all impair BRCA1 HR activity in cells. Furthermore, binding to a set of 5 different phosphopeptides was tested: all causal variants showed phosphopeptide-binding defects and no neutral variant showed such defects. A classification is presented on the basis of mutated BRCT domain solubility, phosphopeptide-binding properties, and VUS HR capacity. These data suggest that HR-defective variants, which present, in addition, BRCT domains either insoluble in bacteria or defective for phosphopeptide binding, lead to an increased cancer risk. Furthermore, the data suggest that variants with a WT HR activity and whose BRCT domains bind with a WT affinity to the 5 phosphopeptides are neutral. The case of variants with WT HR activity and defective phosphopeptide binding should be further characterized, as this last functional defect might be sufficient per se to lead to tumorigenesis. Implications: The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection.
    Mots-clés : B3S, bach1 phosphopeptide, BIM, classification, DBG, dna-damage, domain, functional-analysis, hereditary breast, INTGEN, missense variants, ovarian, repair, structural basis.

  • M. Platel, H. Narassimprakash, D. Ciardo, O. Haccard, et K. Marheineke, « Genome wide decrease of DNA replication eye density at the midblastula transition of Xenopus laevis », Cell Cycle (Georgetown, Tex.), p. 1-15, mai 2019.
    Résumé : During the first rapid divisions of early development in many species, the DNA:cytoplasm ratio increases until the midblastula transition (MBT) when transcription resumes and cell cycles lengthen. S phase is very rapid in early embryos, about 20-30 times faster than in differentiated cells. Using a combination of DNA fiber studies and a Xenopus laevis embryonic in vitro replication system, we show that S phase slows down shortly after the MBT owing to a genome wide decrease of replication eye density. Increasing the dNTP pool did not accelerate S phase or increase replication eye density implying that dNTPs are not rate limiting for DNA replication at the Xenopus MBT. Increasing the ratio of DNA:cytoplasm in egg extracts faithfully recapitulates changes in the spatial replication program in embryos, supporting the hypothesis that titration of soluble limiting factors could explain the observed changes in the DNA replication program at the MBT in Xenopus laevis.
    Mots-clés : DBG, DNA combing, DNA replication, DYNREP, midblastula transition (MBT), replication origins, S-phase, Xenopus laevis.

  • T. Rubio, D. Oyanedel, Y. Labreuche, E. Toulza, X. Luo, M. Bruto, C. Chaparro, M. Torres, J. de Lorgeril, P. Haffner, J. Vidal-Dupiol, A. Lagorce, B. Petton, G. Mitta, A. Jacq, F. Le Roux, G. M. Charrière, et D. Destoumieux-Garzón, « Species-specific mechanisms of cytotoxicity toward immune cells determine the successful outcome of Vibrio infections », Proceedings of the National Academy of Sciences of the United States of America, juin 2019.
    Résumé : Vibrio species cause infectious diseases in humans and animals, but they can also live as commensals within their host tissues. How Vibrio subverts the host defenses to mount a successful infection remains poorly understood, and this knowledge is critical for predicting and managing disease. Here, we have investigated the cellular and molecular mechanisms underpinning infection and colonization of 2 virulent Vibrio species in an ecologically relevant host model, oyster, to study interactions with marine Vibrio species. All Vibrio strains were recognized by the immune system, but only nonvirulent strains were controlled. We showed that virulent strains were cytotoxic to hemocytes, oyster immune cells. By analyzing host and bacterial transcriptional responses to infection, together with Vibrio gene knock-outs, we discovered that Vibrio crassostreae and Vibrio tasmaniensis use distinct mechanisms to cause hemocyte lysis. Whereas V. crassostreae cytotoxicity is dependent on a direct contact with hemocytes and requires an ancestral gene encoding a protein of unknown function, r5.7, V. tasmaniensis cytotoxicity is dependent on phagocytosis and requires intracellular secretion of T6SS effectors. We conclude that proliferation of commensal vibrios is controlled by the host immune system, preventing systemic infections in oysters, whereas the successful infection of virulent strains relies on Vibrio species-specific molecular determinants that converge to compromise host immune cell function, allowing evasion of the host immune system.
    Mots-clés : cytolysis, DBG, dual RNA-seq, pathogenesis, SRRB, T6SS, toxin.

  • S. Scheidecker, S. Bär, C. Stoetzel, V. Geoffroy, B. Lannes, B. Rinaldi, F. Fischer, H. D. Becker, V. Pelletier, C. Pagan, C. Acquaviva-Bourdain, S. Kremer, M. Mirande, C. Tranchant, J. Muller, S. Friant, et H. Dollfus, « Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy », Human Mutation, mai 2019.
    Résumé : Mutations in genes encoding aaRSs (aminoacyl-tRNA synthetases) have been reported in several neurological disorders. KARS is a dual localized lysyl-tRNA synthetase (LysRS) and its cytosolic isoform belongs to the multiple aminoacyl-tRNA synthetase complex (MSC). Biallelic mutations in KARS gene were described in a wide phenotypic spectrum ranging from non-syndromic deafness to complex impairments. Here, we report on a patient with severe neurological and neurosensory disease investigated by whole exome sequencing and found to carry biallelic mutations c.683C>T (p.Pro228Leu) and c.871T>G (p.Phe291Val), the second one being novel, in the KARS gene. The patient presented with an atypical clinical presentation with an optic neuropathy not previously reported. At the cellular level, we show that cytoplasmic KARS was expressed at a lower level in patient cells and displayed decreased interaction with MSC. In vitro, these two KARS variants have a decreased aminoacylation activity compared to wild type KARS, the p.Pro228Leu being the most affected. Our data suggest that dysfunction of cytoplasmic KARS resulted in decreased level of translation of the nuclear encoded lysine rich proteins belonging to the respiratory chain complex, thus impairing mitochondria functions. This article is protected by copyright. All rights reserved.
    Mots-clés : aaRS, DBG, deafness, lysyl-tRNA synthetase, MARS, mitochondrial respiratory chain defect, neurological disorder, optic neuropathy, translation.

  • O. Shukron, V. Piras, D. Noordermeer, et D. Holcman, « Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers », Nature Communications, vol. 10, nᵒ 1, p. 2626, juin 2019.
    Résumé : Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating Domains (TADs). Folding hierarchy and internal organization of TADs is highly dynamic throughout cellular differentiation, and are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency Hi-C encounters within and between TADs into direct loci interactions using cross-links at a given base-pair resolution. We reconstruct three TADs of the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) high order organization into meta-TADs resulting from weak inter-TAD interactions. Finally, the present framework allows to infer transient properties of the chromatin from steady-state statistics embedded in the Hi-C/5C data.
    Mots-clés : CHRODY, DBG.

  • P. Silar, J. - M. Dauget, V. Gautier, P. Grognet, M. Chablat, S. Hermann-Le Denmat, A. Couloux, P. Wincker, et R. Debuchy, « A gene graveyard in the genome of the fungus Podospora comata », Molecular Genetics and Genomics, vol. 294, nᵒ 1, p. 177-190, févr. 2019.
    Résumé : Mechanisms involved in fine adaptation of fungi to their environment include differential gene regulation associated with single nucleotide polymorphisms and indels (including transposons), horizontal gene transfer, gene copy amplification, as well as pseudogenization and gene loss. The two Podospora genome sequences examined here emphasize the role of pseudogenization and gene loss, which have rarely been documented in fungi. Podospora comata is a species closely related to Podospora anserina, a fungus used as model in several laboratories. Comparison of the genome of P. comata with that of P. anserina, whose genome is available for over 10 years, should yield interesting data related to the modalities of genome evolution between these two closely related fungal species that thrive in the same types of biotopes, i.e., herbivore dung. Here, we present the genome sequence of the mat+isolate of the P. comata reference strain T. Comparison with the genome of the mat+isolate of P. anserina strain S confirms that P. anserina and P. comata are likely two different species that rarely interbreed in nature. Despite having a 94-99% of nucleotide identity in the syntenic regions of their genomes, the two species differ by nearly 10% of their gene contents. Comparison of the species-specific gene sets uncovered genes that could be responsible for the known physiological differences between the two species. Finally, we identified 428 and 811 pseudogenes (3.8 and 7.2% of the genes) in P. anserina and P. comata, respectively. Presence of high numbers of pseudogenes supports the notion that difference in gene contents is due to gene loss rather than horizontal gene transfers. We propose that the high frequency of pseudogenization leading to gene loss in P. anserina and P. comata accompanies specialization of these two fungi. Gene loss may be more prevalent during the evolution of other fungi than usually thought.
    Mots-clés : anserina, biodiversity, DBG, DSMC, EDC, Lasiosphaeriaceae, MRP, neanderthal, Podospora anserina, Podospora comata, Pseudogene, pseudogenes, sequence, Sordariales, Speciation.

  • I. J. Silva, S. Barahona, A. Eyraud, D. Lalaouna, N. Figueroa-Bossi, E. Massé, et C. M. Arraiano, « SraL sRNA interaction regulates the terminator by preventing premature transcription termination of rho mRNA », Proceedings of the National Academy of Sciences of the United States of America, vol. 116, nᵒ 8, p. 3042-3051, févr. 2019.
    Résumé : Transcription termination is a critical step in the control of gene expression. One of the major termination mechanisms is mediated by Rho factor that dissociates the complex mRNA-DNA-RNA polymerase upon binding with RNA polymerase. Rho promotes termination at the end of operons, but it can also terminate transcription within leader regions, performing regulatory functions and avoiding pervasive transcription. Transcription of rho is autoregulated through a Rho-dependent attenuation in the leader region of the transcript. In this study, we have included an additional player in this pathway. By performing MS2-affinity purification coupled with RNA sequencing (MAPS), rho transcript was shown to directly interact with the small noncoding RNA SraL. Using bioinformatic in vivo and in vitro experimental analyses, SraL was shown to base pair with the 5'-UTR of rho mRNA upregulating its expression in several growth conditions. This base pairing was shown to prevent the action of Rho over its own message. Moreover, the results obtained indicate that both ProQ and Hfq are associated with this regulation. We propose a model that contemplates the action of Salmonella SraL sRNA in the protection of rho mRNA from premature transcription termination by Rho. Note that since the interaction region between both RNAs corresponds to a very-well-conserved sequence, it is plausible to admit that this regulation also occurs in other enterobacteria.
    Mots-clés : autogenous regulation, bacteria, DBG, escherichia-coli, expression, functional regulatory RNA, gene, hfq, identification, localization, posttranscriptional control, prediction, prokaryotes, RGSP, small noncoding RNA, transcription termination, translation.

  • V. Timofeev, I. Bahtejeva, R. Mironova, G. Titareva, I. Lev, D. Christiany, A. Borzilov, A. Bogun, et G. Vergnaud, « Insights from Bacillus anthracis strains isolated from permafrost in the tundra zone of Russia », PloS One, vol. 14, nᵒ 5, p. e0209140, 2019.
    Résumé : This article describes Bacillus anthracis strains isolated during an outbreak of anthrax on the Yamal Peninsula in the summer of 2016 and independently in Yakutia in 2015. A common feature of these strains is their conservation in permafrost, from which they were extracted either due to the thawing of permafrost (Yamal strains) or as the result of paleontological excavations (Yakut strains). All strains isolated on the Yamal share an identical genotype belonging to lineage B.Br.001/002, pointing to a common source of infection in a territory over 250 km in length. In contrast, during the excavations in Yakutia, three genetically different strains were recovered from a single pit. One strain belongs to B.Br.001/002, and whole genome sequence analysis showed that it is most closely related to the Yamal strains in spite of the remoteness of Yamal from Yakutia. The two other strains contribute to two different branches of A.Br.008/011, one of the remarkable polytomies described so far in the B. anthracis species. The geographic distribution of the strains belonging to A.Br.008/011 is suggesting that the polytomy emerged in the thirteenth century, in combination with the constitution of a unified Mongol empire extending from China to Eastern Europe. We propose an evolutionary model for B. anthracis recent evolution in which the B lineage spread throughout Eurasia and was subsequently replaced by the A lineage except in some geographically isolated areas.
    Mots-clés : DBG, SSFA.

  • H. J. Vetten, D. Knierim, M. S. Rakoski, W. Menzel, E. Maiss, B. Gronenborn, S. Winter, et B. Krenz, « Identification of a novel nanovirus in parsley », Archives of Virology, vol. 164, nᵒ 7, p. 1883-1887, juill. 2019.
    Résumé : Using next-generation sequencing to characterize agents associated with a severe stunting disease of parsley from Germany, we identified a hitherto undescribed virus. We sequenced total RNA and rolling-circle-amplified DNA from diseased plants. The genome sequence of the virus shows that it is a member of the genus Nanovirus, but it lacks DNA-U4. In addition to the seven genomic DNAs of the virus, we identified a second DNA-R and seven distinct alphasatellites associated with the disease. We propose the name parsley severe stunt associated virus (PSSaV) for this novel nanovirus.
    Mots-clés : alphasatellite complex, DBG, encodes, pea, PROMTI, replication, virus.

  • S. Wang, C. Veller, F. Sun, A. Ruiz-Herrera, Y. Shang, H. Liu, D. Zickler, Z. Chen, N. Kleckner, et L. Zhang, « Per-Nucleus Crossover Covariation and Implications for Evolution », Cell, vol. 177, nᵒ 2, p. 326-+, avr. 2019.
    Résumé : Crossing over is a nearly universal feature of sexual reproduction. Here, analysis of crossover numbers on a per-chromosome and per-nucleus basis reveals a fundamental, evolutionarily conserved feature of meiosis: within individual nuclei, crossover frequencies covary across different chromosomes. This effect results from per-nucleus covariation of chromosome axis lengths. Crossovers can promote evolutionary adaptation. However, the benefit of creating favorable new allelic combinations must outweigh the cost of disrupting existing favorable combinations. Covariation concomitantly increases the frequencies of gametes with especially high, or especially low, numbers of crossovers, and thus might concomitantly enhance the benefits of crossing over while reducing its costs. A four-locus population genetic model suggests that such an effect can pertain in situations where the environment fluctuates: hyper-crossover gametes are advantageous when the environment changes while hypo-crossover gametes are advantageous in periods of environmental stasis. These findings reveal a new feature of the basic meiotic program and suggest a possible adaptive advantage.
    Mots-clés : adaptation, advantage, aneuploidy, chromosome axis legngth, chromosome loops, cohesin smc1-beta, crossover, crossover covariation, crossover variance, DBG, evolution of recombination, evolution of sex, frequency, genome-wide recombination rate, individual chromosomes, interference, meiosis, MRP, protein, recombination, sex.

  • A. Zaharia, B. Labedan, C. Froidevaux, et A. Denise, « CoMetGeNe: mining conserved neighborhood patterns in metabolic and genomic contexts », BMC bioinformatics, vol. 20, nᵒ 1, p. 19, janv. 2019.
    Résumé : BACKGROUND: In systems biology, there is an acute need for integrative approaches in heterogeneous network mining in order to exploit the continuous flux of genomic data. Simultaneous analysis of the metabolic pathways and genomic context of a given species leads to the identification of patterns consisting in reaction chains catalyzed by products of neighboring genes. Similar such patterns across several species can reveal their mode of conservation throughout the tree of life. RESULTS: We present CoMetGeNe (COnserved METabolic and GEnomic NEighborhoods), a novel method that identifies metabolic and genomic patterns consisting in maximal trails of reactions being catalyzed by products of neighboring genes. Patterns determined by CoMetGeNe in one species are subsequently employed in order to reflect their degree of conservation across multiple prokaryotic species. These interspecies comparisons help to improve genome annotation and can reveal putative alternative metabolic routes as well as unexpected gene ordering occurrences. CONCLUSIONS: CoMetGeNe is an exploratory tool at both the genomic and the metabolic levels, leading to insights into the conservation of functionally related clusters of neighboring enzyme-coding genes. The open-source CoMetGeNe pipeline is freely available at .
    Mots-clés : BIM, complexes, Conserved interspecies patterns, DBG, evolution, gene, Gene neighborhood, geobacter-sulfurreducens, global alignment, Graph mining, Heterogeneous networks, Heterogeneous networks, identification, Metabolic pathway, operons, organization, pathways, protein-interaction networks, Trail finding.


  • N. Abdollahi, A. Albani, E. Anthony, A. Baud, M. Cardon, R. Clerc, D. Czernecki, R. Conte, L. David, A. Delaune, S. Djerroud, P. Fourgoux, N. Guiglielmoni, J. Laurentie, N. Lehmann, C. Lochard, R. Montagne, V. Myrodia, V. Opuu, E. Parey, L. Polit, S. Privé, C. Quignot, M. Ruiz-Cuevas, M. Sissoko, N. Sompairac, A. Vallerix, V. Verrecchia, M. Delarue, R. Guérois, Y. Ponty, S. Sacquin-Mora, A. Carbone, C. Froidevaux, S. Le Crom, O. Lespinet, M. Weigt, S. Abboud, J. Bernardes, G. Bouvier, C. Dequeker, A. Ferré, P. Fuchs, G. Lelandais, P. Poulain, H. Richard, H. Schweke, E. Laine, et A. Lopes, « Meet-U: Educating through research immersion », PLoS computational biology, vol. 14, nᵒ 3, p. e1005992, mars 2018.
    Résumé : We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4-5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes "coopetition," as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master's students in bioinformatics and modeling, with protein-protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at
    Mots-clés : AMIG, B3S, BIM, DBG.

  • C. Apel, J. Bignon, M. C. Garcia-Alvarez, S. Ciccone, P. Clerc, I. Grondin, E. Girard-Valenciennes, J. Smadja, P. Lopes, M. Frederich, F. Roussi, T. Meinnel, C. Giglione, et M. Litaudon, « N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoe (L.) L. f. subsp. bentzoe », Fitoterapia, vol. 131, p. 91-95, nov. 2018.
    Résumé : N-myristoylation (Myr) is an eukaryotic N-terminal co- or post-translational protein modification in which the enzyme N-myristoyltransferase (NMT) transfers a fatty acid (C14:0) to the N-terminal glycine residues of several cellular key proteins. Depending on the cellular context, NMT may serve as a molecular target in anticancer or anti-infectious therapy, and drugs that inhibit this enzyme may be useful in the treatment of cancer or infectious diseases. As part of an on-going project to identify natural Homo sapiens N-myristoyltransferase 1 inhibitors (HsNMT1), two ellagitannins, punicalagin (1) and isoterchebulin (2), along with eschweilenol C (3) and ellagic acid (4) were isolated from the bark of Terminalia bentzoe (L.) L. f. subsp. bentzoe. Their structures were determined by means of spectroscopic analyses and comparison with literature data. Punicalagin (1) and isoterchebulin (2) showed significant inhibitory activity towards HsNMT1, and also against Plasmodium falciparum NMT (PfNMT) both in vitro and in cellulo, opening alternative paths for new NMT inhibitors development. This is the first report identifying natural products from a botanical source as inhibitors of HsNMT and PfNMT.
    Mots-clés : acylation, bark, Combretaceae, DBG, Ellagitannins, hydrolyzable tannins, in-vitro, Isoterchebulin, malaria, myristoylation, N-myristoyltransferase, nmr assignments, PROMTI, Punicalagin, Terminalia bentzoe subsp. bentzoe.

  • J. - M. Arbona, A. Goldar, O. Hyrien, A. Arneodo, et B. Audit, « The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation », eLife, vol. 7, juin 2018.
    Résumé : The time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris. We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics.
    Mots-clés : chromosomes, computational biology, DBG, gene expression, GTR, human, S. cerevisiae, systems biology.

  • M. Benchouaia, H. Ripoche, M. Sissoko, A. Thiébaut, J. Merhej, T. Delaveau, L. Fasseu, S. Benaissa, G. Lorieux, L. Jourdren, S. Le Crom, G. Lelandais, E. Corel, et F. Devaux, « Comparative Transcriptomics Highlights New Features of the Iron Starvation Response in the Human Pathogen Candida glabrata », Frontiers in Microbiology, vol. 9, p. 2689, 2018.
    Résumé : In this work, we used comparative transcriptomics to identify regulatory outliers (ROs) in the human pathogen Candida glabrata. ROs are genes that have very different expression patterns compared to their orthologs in other species. From comparative transcriptome analyses of the response of eight yeast species to toxic doses of selenite, a pleiotropic stress inducer, we identified 38 ROs in C. glabrata. Using transcriptome analyses of C. glabrata response to five different stresses, we pointed out five ROs which were more particularly responsive to iron starvation, a process which is very important for C. glabrata virulence. Global chromatin Immunoprecipitation and gene profiling analyses showed that four of these genes are actually new targets of the iron starvation responsive Aft2 transcription factor in C. glabrata. Two of them (HBS1 and DOM34b) are required for C. glabrata optimal growth in iron limited conditions. In S. cerevisiae, the orthologs of these two genes are involved in ribosome rescue by the NO GO decay (NGD) pathway. Hence, our results suggest a specific contribution of NGD co-factors to the C. glabrata adaptation to iron starvation.
    Mots-clés : Aft, ascomycete fungi, BIM, ChIP-seq, comparative genomics, DBG, evolution, gene regulatory networks, glutathione transferase, messenger-rna, monothiol glutaredoxins, NO GO decay, oxidative stress-response, schistosoma-mansoni, selenite toxicity, yeast, yeast saccharomyces-cerevisiae.

  • S. Bhullar, C. D. Wilkes, O. Arnaiz, M. Nowacki, L. Sperling, et E. Meyer, « A mating-type mutagenesis screen identifies a zinc-finger protein required for specific DNA excision events in Paramecium », Nucleic Acids Research, vol. 46, nᵒ 18, p. 9550-9562, oct. 2018.
    Résumé : In the ciliate Paramecium tetraurelia, functional genes are reconstituted during development of the somatic macronucleus through the precise excision of similar to 45 000 single-copy Internal Eliminated Sequences (IESs), thought to be the degenerate remnants of ancient transposon insertions. Like introns, IESs are marked only by a weak consensus at their ends. How such a diverse set of sequences is faithfully recognized and precisely excised remains unclear: specialized small RNAs have been implicated, but in their absence up to similar to 60% of IESs are still correctly excised. To get further insight, we designed a mutagenesis screen based on the hypersensitivity of a specific excision event in the mtA gene, which determines mating types. Unlike most IES-containing genes, the active form of mtA is the unexcised one, allowing the recovery of hypomorphic alleles of essential IES recognition/excision factors. Such is the case of one mutation recovered in the Piwi gene PTIWI09, a key player in small RNA-mediated IES recognition. Another mutation identified a novel protein with a C2H2 zinc finger, mtGa, which is required for excision of a small subset of IESs characterized by enrichment in a 5-bp motif. The unexpected implication of a sequence-specific factor establishes a new paradigm for IES recognition and/or excision.
    Mots-clés : ANGE, DBG, developmental excision, differentiation, discovery, genetic-analysis, GTR, internal eliminated sequences, macronuclear development, MICMAC, piwi proteins, rearrangements, rna pathways, tetraurelia.

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