Principles of Meiotic Chromosome Assembly

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 elucidate how this elaborate three-dimensional chromosome organisation is underpinned by genomic sequence in Saccharomyces cerevisiae. Entering meiosis, 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 limited by barriers, yet are patterned by convergent transcription rather than binding of the mammalian interphase factor, CTCF, which is absent in S. cerevisiae—thereby both challenging and extending current paradigms of local chromosome organisation. 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. Overall design: This submission contains the following Hi-C experiments: meiotic timecourse samples of wt (0h, 2h, 3h, 4h, 5h, 6h, 8h) main figure; meiotic timecourse samples of wt (2h, 3h, 4h, 6h) supplementary figure; 2 biological replicates of the following genotypes grown for 8h in sporulation media, accumulating in pachytene: ndt80-d; rec8-d ndt80-d; zip1-d ndt80-d; 1 replicate of hop1-d ndt80-d. 2 biological replicates of wt diploid cells grown exponentially and arrested in G2/M by addition of the spindel poison nocodazole.