多梳蛋白 SCML2 促进 H3K27me3 在雄性生殖细胞中建立双价结构域。

Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline.

机构信息

Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.

Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.

出版信息

Proc Natl Acad Sci U S A. 2018 May 8;115(19):4957-4962. doi: 10.1073/pnas.1804512115. Epub 2018 Apr 23.

Abstract

Repressive H3K27me3 and active H3K4me2/3 together form bivalent chromatin domains, molecular hallmarks of developmental potential. In the male germline, these domains are thought to persist into sperm to establish totipotency in the next generation. However, it remains unknown how H3K27me3 is established on specific targets in the male germline. Here, we demonstrate that a germline-specific Polycomb protein, SCML2, binds to H3K4me2/3-rich hypomethylated promoters in undifferentiated spermatogonia to facilitate H3K27me3. Thus, SCML2 establishes bivalent domains in the male germline of mice. SCML2 regulates two major classes of bivalent domains: Class I domains are established on developmental regulator genes that are silent throughout spermatogenesis, while class II domains are established on somatic genes silenced during late spermatogenesis. We propose that SCML2-dependent H3K27me3 in the male germline prepares the expression of developmental regulator and somatic genes in embryonic development.

摘要

抑制性的 H3K27me3 和活性的 H3K4me2/3 共同形成具有双重染色质结构域,这是发育潜能的分子标志。在雄性生殖细胞中,这些结构域被认为在精子中持续存在,以在下一代中建立全能性。然而,H3K27me3 如何在雄性生殖细胞中的特定靶标上建立仍然未知。在这里,我们证明了一种生殖细胞特异性的多梳蛋白 SCML2 结合到未分化精原细胞中富含 H3K4me2/3 的低甲基化启动子上,以促进 H3K27me3。因此,SCML2 在小鼠的雄性生殖细胞中建立了双重结构域。SCML2 调节两类主要的双重结构域:I 类结构域建立在整个精子发生过程中沉默的发育调节剂基因上,而 II 类结构域建立在晚期精子发生过程中沉默的体细胞基因上。我们提出,雄性生殖细胞中 SCML2 依赖性的 H3K27me3 为胚胎发育中发育调节剂和体细胞基因的表达做准备。

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