PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.
PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.
复制标题
DOI：
10.7554/elife.21064
复制
发表时间：
2017-03-17
期刊：
影响因子：
7.7
通讯作者：
Koseki H
中科院分区：
文献类型：
--
作者：
Endoh M;Endo TA;Shinga J;Hayashi K;Farcas A;Ma KW;Ito S;Sharif J;Endoh T;Onaga N;Nakayama M;Ishikura T;Masui O;Kessler BM;Suda T;Ohara O;Okuda A;Klose R;Koseki H
环指蛋白PCGF 6（polycomb group ring finger 6）与RING 1A/B和E2 F6相关因子相互作用，形成称为PCGF 6-PRC 1的非典型PRC 1（polycomb repressive complex 1）。在这里，我们证明了PCGF 6-PRC 1通过募集RING 1B和介导组蛋白H2 A的下游单泛素化来抑制PRC 1靶基因的子集。PCGF 6-PRC 1结合位点高度富集小鼠胚胎干细胞（ESC）中生殖细胞相关基因的启动子。在ESC中Pcgf 6的条件性消融导致这些生殖细胞相关基因的强烈去抑制，进而影响细胞生长和活力。我们还发现PCGF 6在植入前和植入期小鼠胚胎发育中的作用。我们进一步表明，转录因子MAX和MGA的异源二聚体招募PCGF 6靶位点。因此，PCGF 6将MAX/MGA复合物的序列特异性靶识别与多能干细胞中生殖细胞特异性基因的PRC 1依赖性转录沉默联系起来。DOI：http://dx.doi.org/10.7554/eLife.21064.001网站
The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells. DOI: http://dx.doi.org/10.7554/eLife.21064.001