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Principles of chromosome organization for meiotic recombination
Molecular Cell ( IF 16.0 ) Pub Date : 2024-04-23 , DOI: 10.1016/j.molcel.2024.04.001
Mathilde Biot , Attila Toth , Christine Brun , Leon Guichard , Bernard de Massy , Corinne Grey

In meiotic cells, chromosomes are organized as chromatin loop arrays anchored to a protein axis. This organization is essential to regulate meiotic recombination, from DNA double-strand break (DSB) formation to their repair. In mammals, it is unknown how chromatin loops are organized along the genome and how proteins participating in DSB formation are tethered to the chromosome axes. Here, we identify three categories of axis-associated genomic sites: PRDM9 binding sites, where DSBs form; binding sites of the insulator protein CTCF; and H3K4me3-enriched sites. We demonstrate that PRDM9 promotes the recruitment of MEI4 and IHO1, two proteins essential for DSB formation. In turn, IHO1 anchors DSB sites to the axis components HORMAD1 and SYCP3. We discovered that IHO1, HORMAD1, and SYCP3 are associated at the DSB ends during DSB repair. Our results highlight how interactions of proteins with specific genomic elements shape the meiotic chromosome organization for recombination.



中文翻译:

减数分裂重组的染色体组织原理

在减数分裂细胞中,染色体被组织为锚定在蛋白质轴上的染色质环阵列。该组织对于调节减数分裂重组(从 DNA 双链断裂 (DSB) 形成到修复)至关重要。在哺乳动物中,尚不清楚染色质环如何沿着基因组组织,以及参与 DSB 形成的蛋白质如何与染色体轴相连。在这里,我们确定了三类轴相关基因组位点:PRDM9 结合位点,DSB 在此形成;绝缘体蛋白 CTCF 的结合位点;和 H3K4me3 富集位点。我们证明 PRDM9 促进 MEI4 和 IHO1 的募集,这两种蛋白质对于 DSB 形成至关重要。反过来,IHO1 将 DSB 位点锚定到轴组件 HORMAD1 和 SYCP3。我们发现在 DSB 修复过程中 IHO1、HORMAD1 和 SYCP3 在 DSB 末端相关联。我们的结果强调了蛋白质与特定基因组元件的相互作用如何塑造减数分裂染色体组织以进行重组。

更新日期:2024-04-23
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