Principles of meiotic chromosome assembly revealed in S. cerevisiae

Principles of meiotic chromosome assembly revealed in S. cerevisiae
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DOI:
10.1038/s41467-019-12629-0
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发表时间:
2019-10
影响因子:
16.6
通讯作者:
S. Schalbetter;G. Fudenberg;J. Baxter;K. Pollard;Matthew J. Neale
S. Schalbetter;G. Fudenberg;J. Baxter;K. Pollard;Matthew J. Neale
中科院分区:
综合性期刊1区
文献类型:
--
作者:
S. Schalbetter;G. Fudenberg;J. Baxter;K. Pollard;Matthew J. Neale

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在减数分裂前期,染色体组织成一系列从蛋白质轴发出的染色质环,但组装机制仍不清楚。在这里,我们使用酿酒酵母来探索这种复杂的三维染色体组织如何与基因组序列联系起来。当细胞进入减数分裂时,我们观察到出现了强烈的依赖于粘连蛋白的网格状 Hi-C 相互作用模式,让人想起哺乳动物的间期组织,但具有不同的调节。减数分裂模式与环挤出的模拟一致,其中生长受屏障限制,其中扩展环的异质群体沿着染色体发育。重要的是,CTCF(在哺乳动物间期中施加类似特征的因子)在 S 中不存在。酿酒酵母,表明屏障形成的替代机制。虽然网格状相互作用独立于减数分裂染色体突触而出现,但突触本身会产生额外的压缩,根据端粒接近度和染色体大小而有不同的成熟程度。总的来说,我们的结果阐明了染色体组装的基本原理,并证明了粘连蛋白在这一进化保守过程中的重要作用。
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 useSaccharomyces cerevisiaeto 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 inS. 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.