Bacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. The linear chromosome includes a central region harboring core genes, as well as extremities enriched in specialized metabolite biosynthetic gene clusters. Here, we show that chromosome structure in Streptomyces ambofaciens correlates with genetic compartmentalization during exponential phase. Conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends tend to be transcriptionally quiescent compartments with different structural features. The onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture, from a rather ‘open’ to a ‘closed’ conformation, in which highly expressed specialized metabolite biosynthetic genes form new boundaries. Thus, our results indicate that the linear chromosome of S. ambofaciens is partitioned into structurally distinct entities, suggesting a link between chromosome folding, gene expression and genome evolution.

Streptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear chromosome 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 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.

Streptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear chromosome 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 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.

Objectives Transcriptional regulatory modules are usually modelled via a network, in which nodes correspond to genes and edges correspond to regulatory associations between them. In the model yeast Saccharomyces cerevisiae, the topological properties of such a network are well-described (distribution of degrees, hierarchical levels, organization in network motifs, etc.). To go further on this, our aim was to search for additional information resulting from the new combination of classical representations of transcriptional regulatory networks with more realistic models of the spatial organization of S. cerevisiae genome in the nucleus. Results Taking advantage of independent studies with high-quality datasets, i.e. lists of target genes for specific transcription factors and chromosome positions in a three dimensional space representing the nucleus, particular spatial co-localizations of genes that shared common regulatory mechanisms were searched. All transcriptional modules of S. cerevisiae, as described in the latest release of the YEASTRACT database were analyzed and significant biases toward co-localization for a few sets of target genes were observed. To help other researchers to reproduce such analysis with any list of genes of their interest, an interactive web tool called 3D-Scere (https://3d-scere.ijm.fr/) is provided.

The functions of eukaryotic chromosomes and their spatial architecture in the nucleus are reciprocally dependent. Hi-C experiments are routinely used to study chromosome 3D organization by probing chromatin interactions. Standard representation of the data has relied on contact maps that show the frequency of interactions between parts of the genome. In parallel, it has become easier to build 3D models of the entire genome based on the same Hi-C data, and thus benefit from the methodology and visualization tools developed for structural biology. 3D modeling of entire genomes leverages the understanding of their spatial organization. However, this opportunity for original and insightful modeling is under exploited. In this paper, we show how seeing the spatial organization of chromosomes can bring new perspectives to Hi-C data analysis. We assembled state-of-the-art tools into a workflow that goes from Hi-C raw data to fully annotated 3D models and we re-analysed public Hi-C datasets available for three fungal species. Besides the well-described properties of the spatial organization of their chromosomes (Rabl conformation, hypercoiling and chromosome territories), our 3D models highlighted i) in Saccharomyces cerevisiae, the backbones of the cohesin anchor regions, which were aligned all along the chromosomes, ii) in Schizosaccharomyces pombe, the oscillations of the coiling of chromosome arms throughout the cell cycle and iii) in Neurospora crassa, the massive relocalization of histone marks in mutants of heterochromatin regulators. 3D modeling of the chromosomes brings new opportunities for visual integration. This holistic perspective supports intuition and lays the foundation for building new concepts.