Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells
Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells
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DOI：
10.1016/j.celrep.2019.12.057
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发表时间：
2020-01-21
期刊：
影响因子：
8.8
通讯作者：
Klose, Robert J.
中科院分区：
文献类型：
--
作者：
Rhodes, James D. P.;Feldmann, Angelika;Klose, Robert J.
染色体组织如何与基因组功能相关仍然知之甚少。粘附素、环挤出和CCCTC结合因子(CTCF)已被提出用来创建拓扑关联结构域(TADS)来调节基因表达。在这里，我们检查了缺乏粘附素的胚胎干细胞的染色体构象，并发现，与其他类型的细胞一样，粘附素是产生TADS和调节A/B划分所必需的。然而，在缺乏粘附素的情况下，我们发现了一系列持续存在的长距离染色体相互作用。这些区域对应于基因组中被多梳抑制系统占据的区域，并依赖于Prc1。重要的是，我们发现粘附素可以抵消这些多梳依赖的相互作用，但不能抵消超级增强剂之间的相互作用。这种破坏活动独立于CTCF和绝缘，似乎通过多梳系统调节基因抑制。因此，我们发现粘附素破坏了多梳依赖的染色体相互作用，从而调节了胚胎干细胞中的基因表达。
How chromosome organization is related to genome function remains poorly understood. Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) have been proposed to create topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find, as in other cell types, that cohesin is required to create TADs and regulate A/B compartmentalization. However, in the absence of cohesin, we identify a series of long-range chromosomal interactions that persist. These correspond to regions of the genome occupied by the polycomb repressive system and are dependent on PRC1. Importantly, we discover that cohesin counteracts these polycomb-dependent interactions, but not interactions between super-enhancers. This disruptive activity is independent of CTCF and insulation and appears to modulate gene repression by the polycomb system. Therefore, we discover that cohesin disrupts polycomb-dependent chromosome interactions to modulate gene expression in embryonic stem cells.