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首页> 外文期刊>Molecular and Cellular Biology >RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells
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RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells

机译：RYBP抑制小鼠胚胎干细胞内源性逆转录病毒和植入前和胚系特定基因。

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Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Using ES cells conditionally deficient in RYBP, we found that RYBP is not required for maintenance of the ES cell state, although mutant cells differentiate abnormally. Genome-wide chromatin association studies showed RYBP binding to promoters of Polycomb targets, although its presence is dispensable for gene repression. We discovered, using Eed-knockout (KO) ES cells, that RYBP binding to promoters was independent of H3K27me3. However, recruiting of PRC1 subunits Ring1B and Mel18 to their targets was not altered in the absence of RYBP. In contrast, we have found that RYBP efficiently represses endogenous retroviruses (murine endogenous retrovirus [MuERV] class) and preimplantation (including zygotic genome activation stage)- and germ line-specific genes. These observations support a selective repressor activity for RYBP that is dispensable for Polycomb function in the ES cell state. Also, they suggest a role for RYBP in epigenetic resetting during preimplantation development through repression of germ line genes and PcG targets before formation of pluripotent epiblast cells.
机译：聚梳抑制复合物（PRC）是胚胎干（ES）细胞功能的重要染色质调节剂。 RYBP结合Polycomb H2A单泛素连接酶Ring1A和Ring1B，并已被建议协助PRC定位到其目标。此外，RYBP的组成型失活阻止了ES细胞的形成。使用条件上缺乏RYBP的ES细胞，我们发现RYBP并不是维持ES细胞状态所必需的，尽管突变细胞异常分化。全基因组染色质缔合研究显示，RYBP与Polycomb靶标的启动子结合，尽管它的存在对于基因抑制是必不可少的。我们发现，使用Eed基因敲除（KO）ES细胞，RYBP与启动子的结合独立于H3K27me3。但是，在没有RYBP的情况下，PRC1亚基Ring1B和Mel18募集至其靶标并没有改变。相反，我们发现RYBP有效抑制内源性逆转录病毒（鼠内源性逆转录病毒[MuERV]类）和植入前（包括合子基因组激活阶段）和种系特异性基因。这些观察结果支持RYBP的选择性阻遏物活性，这对于ES细胞状态下的Polycomb功能是必不可少的。此外，他们还提出了RYBP在胚前发育过程中通过形成多能表皮细胞抑制种系基因和PcG靶标而在表观遗传复位中的作用。

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