RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells
RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells
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DOI：
10.1128/mcb.06441-11
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发表时间：
2012-03-01
影响因子：
5.3
通讯作者：
Vidal, Miguel
中科院分区：
文献类型：
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作者：
Hisada, Kaori;Sanchez, Carmen;Vidal, Miguel
多梳抑制复合物（PRCs）是胚胎干细胞（ES）功能的重要染色质调节因子。RYBP结合Polycomb H2A单泛素连接酶Ring1A和Ring1B，并被认为有助于PRC定位于其靶标。此外，RYBP的组成性失活排除了ES细胞的形成。使用条件性缺乏RYBP的ES细胞，我们发现RYBP不是维持ES细胞状态所必需的，尽管突变细胞分化异常。全基因组染色质关联研究表明，RYBP结合的启动子Polycomb目标，虽然它的存在是不确定的基因阻遏。我们发现，使用Eed敲除（KO）ES细胞，RYBP与启动子的结合不依赖于H3K27me3。然而，PRC1亚基Ring1B和Mel 18的募集在RYBP不存在的情况下没有改变。相反，我们发现RYBP有效地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）和生殖系特异性基因。这些观察结果支持RYBP的选择性阻遏活性，其在ES细胞状态下与Polycomb功能无关。此外，他们建议的作用，RYBP在植入前发育过程中的表观遗传重置通过生殖系基因和PcG的目标形成多能外胚层细胞之前的镇压。
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.