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Home > Departments > Genome Biology > Daan NOORDERMEER : Chromatin Dynamics

Group Chromatin Dynamics

How does the organization of chromatin influence the activity of genes? The Chromatin Dynamics group studies this question by linking epigenetics and 3D DNA structure using systems biology approaches in four projects: (1) dynamics of DNA organization during the mammalian life cycle and in cancer, (2) 3D genome organization of epigenetic domains for gene regulation, (3) coordinated regulation of gene networks by epigenetic mechanisms and (4) variability of 3D genome organization within the cell population and its influence on single-cell gene expression.

Team Members

Team_2018

Daan Noordermeer – Team leader
Marine Beinat – Visiting scientist INRA
Sébastien Bloyer – Professor University Paris-Sud
Li-Hsin Chang – Post-doctoral researcher
Mélanie Miranda – Research Engineer
Benoit Moindrot –
           Assistant professor University Paris-Sud
Laura Moniot Perron – PhD student
Charbel Souaid – PhD student


Research projects

The Chromatin Dynamics Group started its operations in 2014. We study how the molecular structure of DNA regulates the activity of the genes in mammalian genomes. Particularly, we are interested in the regulatory functions of epigenetic mechanisms, the 3D organization of the genome, and how these two components act together. To answer these questions, we study mouse cells using a combination of (epi)genomics (ChIP-seq, Hi-C, 4C-seq), imaging (conventional and confocal fluorescent microscopy), bio-chemical approaches and bio-informatics.

The group is headed by Daan Noordermeer. The research of Sébastien Bloyer, professor in epigenetics at the University Paris-Saclay, is also part of the group.

The research is divided into four thematics:


Dynamics of DNA structure during the mammalian life cycle and in cancer
PI: Daan Noordermeer

Mammalian cells have different proliferative capacity depending on the life cycle. Early embryonic stem cells are highly proliferative and are able to differentiate into any cellular identity. Later stage adult and aged cells lose both their proliferative and differentiating capacity. Cancer cells also mostly lack the differentiating capacity, yet they have reestablished a high level of proliferation.

In cells from different stages of the life cycle, specific patterns of chromatin structure and 3D genome organization can be observed. Currently though, a systematic comparison between all these time-points is missing. We are taking a systems biology approach using bioinformatics-based modeling to link global organization of the nucleus (confocal microscopy), patterns of histone modifications (ChIP-seq) and high-resolution 3D genome organization (Hi-C) in early embryonic cells, adult cells, aged cells and cancer cells.


3D genome organization of epigenetic domains for gene regulation
PI: Daan Noordermeer

The parts of the genome that are marked by the same histone modifications can adopt compartmentalized 3D configurations (PMID: 21998387). Though the pervasiveness of this phenomenon is nowadays well established (PMID: 25497547), its actual function remains poorly understood.

We are using novel strategies to precisely edit the presence of histone modifications at defined sites in the genome. Using a combination of ChIP, 4C-seq and highly-sensitive transcriptional analyses (TaqMan-qPCR) we study how these changes influence 3D chromatin structure and what is the effect on transcriptional activity and regulation.


Coordinated regulation of gene networks by epigenetic mechanisms
PI: Sébastien Bloyer

Many genes involved in common biological processes exhibit synchronized transcriptional regulation, despite being scattered across the genome. We study if epigenetic mechanisms and nuclear organization help to coordinate the regulation of these gene networks (PMID: 25801168).

The majority of cell metabolism is dedicated to ribosome biogenesis, therefore this process must be fine-tuned to maintain cellular homeostasis. We analyze the epigenetic regulatory networks that enable the synchronized expression of the hundreds of genes involved in ribosome biogenesis in mammals. Using a combination of RNA-seq, ChIP-seq and Hi-C we analyze changes in these regulatory gene networks during carcinogenesis and other metabolic disturbance, during ES cell differentiation and in aging.


Variability of 3D genome organization within the cell population and its influence on single-cell gene expression
PI: Daan Noordermeer

Individual cells within the same population can display drastically different 3D genome organization. Currently though, we lack the tools to study this variation at ultra-high resolution on the level of individual genes, and as a consequence, to link this variation to transcriptional regulation.

We are developing new, high-throughput sequencing-based technology to study the variation in 3D genome organization at the single-cell level. These tools allow us to link this variation to the robustness of gene regulatory mechanisms and to the choice of cellular identity.


Recent publications


- Vieux-Rochas, et al. (2015) Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain. PNAS 112, 4672-4677 Link
- Noordermeer, D., et al. (2014) Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci. eLife 3, e02557 Link
- Coléno-Costes, A., et al (2012) New partners in regulation of gene expression : the enhancer of Trithorax and Polycomb Corto interacts with methylated ribosomal protein l12 via its chromodomain. PLoS Genet 8, e1003006 Link


Key words

Chromatin structure, Epigenetics, 3D genome organization, Gene regulation, Hi-C, 4C-seq, ChIP-seq, Bioinformatics


Contact


NOORDERMEER Daan [Researcher - CNRS]
Chromatin Dynamics [Leader]
01 69 82 31 38 Gif - Bât 26


BLOYER Sébastien [Professor - UPSud]
Chromatin Dynamics
01 69 82 32 01 Gif - Bât 26

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