Abstract
During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process.
Highlights
During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear
Eukaryotic chromosomes are broken, repaired and paired with their homologues followed by two rounds of segregation—a series of events accompanied by dynamic structural changes of the chromosomes (Fig. 1a, top)
Most prominent is the paired arrangement of pachytene chromosomes into a dense array of chromatin loops emanating from proteinaceous axes linked by a central core, the synaptonemal complex (SC), which is highly conserved across eukaryotes[2,3]
Summary
Chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. 3C methods were originally applied to assay chromosome conformation in S. cerevisiae, including during meiosis[12] They are widely used across a range of organisms and cellular contexts to link 3D organisation directly with genomic sequence[13], revealing important roles of the Structural Maintenance of Chromosomes (SMCs) cohesin and condensin in genomic organisation[14,15], where they likely mediate chromosome compaction via the process of loop extrusion[16]. In S. cerevisiae, Hi–C with a synthetically re-designed chromosome found low levels of interhomologue contacts, and increased insulation at Rec[8] sites[20] It remains to be determined whether cohesin is required for the formation of meiotic chromosome structure, as measured by Hi-C, and what mechanisms organise meiotic chromosomes
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