Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

Streptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear genome is partitioned into a central region harboring core genes and two extremities enriched in specialized metabolite biosynthetic gene clusters (SMBGCs). The molecular mechanisms governing structure and function of these compartmentalized genomes remain mostly unknown. Here we show that in exponential phase, chromosome structure correlates with genetics compartmentalization: conserved, large and highly transcribed genes form boundaries that segment the central part of the genome 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. ambofacien's linear chromosome is partitioned into structurally distinct entities, indicating a link between chromosome folding, gene expression and genome evolution Overall design: Analysis of chromosome conformation and transcriptome of Streptomyces ambofaciens ATCC 23877 during metabolic differentiation