FACT mediates cohesin function on chromatin
FACT mediates cohesin function on chromatin
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DOI：
10.1038/s41594-019-0307-x
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发表时间：
2019-10-01
影响因子：
16.8
通讯作者：
Aragon, Luis
中科院分区：
文献类型：
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作者：
Garcia-Luis, Jonay;Lazar-Stefanita, Luciana;Aragon, Luis
粘连蛋白是基因组结构的调节剂，在姐妹染色单体凝聚和染色体压缩中发挥作用。 DNA 上粘连蛋白复合物的募集和移动性受到核小体的限制。在这里，我们证明了粘连蛋白在染色体组织中的作用需要酿酒酵母中的组蛋白伴侣 FACT（“促进染色质转录”）。我们发现 FACT 直接与粘连蛋白相互作用，并且是其在染色质上定位的动态需要。中期细胞中 FACT 的缺失会阻止粘连蛋白在中心周区域的积累，并导致染色体臂上的结合减少。使用 Hi-C 技术，我们发现在缺乏 FACT 的情况下，G1 和中期染色体中依赖于粘连蛋白的 TAD（拓扑相关域）样结构会减少。尽管观察到染色体分离失败，但在 FACT 耗尽的细胞中，姐妹染色单体的内聚力是完整的。我们的数据表明，FACT 有助于粘连蛋白依赖性 TAD 的形成，从而揭示了该复合物在间期和有丝分裂染色体折叠期间核组织中的新作用。
Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes. Here, we show that the role of cohesin in chromosome organization requires the histone chaperone FACT ('facilitates chromatin transcription') in Saccharomyces cerevisiae. We find that FACT interacts directly with cohesin, and is dynamically required for its localization on chromatin. Depletion of FACT in metaphase cells prevents cohesin accumulation at pericentric regions and causes reduced binding on chromosome arms. Using the Hi-C technique, we show that cohesin-dependent TAD (topological associated domain)-like structures in G1 and metaphase chromosomes are reduced in the absence of FACT. Sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our data show that FACT contributes to the formation of cohesin-dependent TADs, thus uncovering a new role for this complex in nuclear organization during interphase and mitotic chromosome folding.