Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.
Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.
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DOI：
10.1038/ng.3393
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发表时间：
2015-10
期刊：
影响因子：
30.8
通讯作者：
Elderkin S
中科院分区：
文献类型：
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作者：
Schoenfelder S;Sugar R;Dimond A;Javierre BM;Armstrong H;Mifsud B;Dimitrova E;Matheson L;Tavares-Cadete F;Furlan-Magaril M;Segonds-Pichon A;Jurkowski W;Wingett SW;Tabbada K;Andrews S;Herman B;LeProust E;Osborne CS;Koseki H;Fraser P;Luscombe NM;Elderkin S
Polycomb抑制复合物PRC 1和PRC 2通过沉默谱系特异性发育调节基因来维持胚胎干细胞（ESC）的多能性。新出现的证据表明，Polycomb复合物通过控制空间基因组组织发挥作用。我们表明，PRC 1的功能作为一个主调节ESC基因组结构的组织基因在三维相互作用网络。最强的空间网络由四个Hox簇和早期发育转录因子基因组成，其中大多数与平衡增强子接触。Polycomb抑制的去除导致Hox网络中启动子-启动子接触的破坏。与此相反，启动子-增强子的接触得以维持，伴随着网络增强子处活性染色质签名的广泛获得和网络基因的显著转录上调。因此，PRC 1在物理上将发育转录因子基因及其增强子限制在沉默但稳定的空间网络中。我们建议，从这个空间网络的基因选择性释放的基础细胞命运规范在早期胚胎发育。
The Polycomb Repressive Complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organisation. We show that PRC1 functions as a master regulator of ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox network. In contrast, promoter-enhancer contacts are maintained, accompanied by widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional up-regulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that selective release of genes from this spatial network underlies cell fate specification during early embryonic development.