Streptomyces are amongst the most prolific producers of specialized metabolites (e.g. antibiotics and pigments) with applications in medicine, agriculture and the food industry. They present features uncommon among bacteria such as a linear chromosome and a complex developmental cycle (uni- to multi-cellular transition, sporulation, metabolic differentiation leading to antibiotic production). Moreover, their genome represents a paroxysm of genetic compartmentalization, with a central region harboring core genes, being often essential, and two extremities enriched in conditionally adaptive genes such as specialized metabolite biosynthetic gene clusters. We recently reported a correlation between this genetic compartmentalization and genome folding, and provide an important bridge between evolutionary and molecular processes that shape the chromosome. We recently showed that in exponential phase, chromosome structure correlates with genetic compartmentalization: conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends are transcriptionally, largely quiescent compartments with different structural features. Onset of metabolic differentiation is accompanied by remodeling of chromosome architecture from an ‘open’ to a rather ‘closed’ conformation, in which the SMBGCs are expressed forming new boundaries. Altogether, our results reveal that S. ambofaciens’ linear chromosome is partitioned into structurally distinct entities, indicating a link between chromosome folding, gene expression and genome evolution. We now want to identify the factors that determine these chromatin dynamics. Our project is likely to allow breakthroughs in the knowledge of Streptomyces chromatin dynamics, potentially allowing the identification of new actors involved in the regulation of antibiotic production.