Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin.
Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin.
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DOI：
10.1093/nar/gkad479
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发表时间：
2023-07-21
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
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作者：
精子染色质保留少量组蛋白，精子的染色质状态反映了下一代的基因表达程序。然而，父系表观遗传信息是如何通过精子染色质传递的，这在很大程度上仍然是未知的。在这里，我们提出了一种新的父系表观遗传小鼠模型，其中Polycomb抑制复合体2 （PRC2）介导的抑制性H3K27me3的沉积在父系种系中被减弱。利用改良的睾丸精子辅助生殖技术，我们通过在带有其他活性标记H3K4me2/3的二价启动子上建立H3K27me3来调节种系基因表达的Polycomb蛋白SCML2缺失小鼠，从而挽救了不育小鼠。我们分析了睾丸精子和附睾精子的表观基因组状态（H3K27me3和H3K4me3），证明精子的附睾模式表观基因组已经在睾丸精子中建立，并且这一过程需要SCML2。在具有野生型基因型的x连锁scml2敲除小鼠的F1雄性中，在精子发生过程中，雄性种系中的基因表达失调。这些失调基因是F0精子中scml2介导的H3K27me3的靶标。此外，在突变体衍生的野生型F1着床前胚胎中观察到基因表达失调。总之，我们提出的功能证据表明，经典的表观遗传调节剂Polycomb通过精子染色质介导父系表观遗传。
Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal epigenetic inheritance, in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-type F1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin.
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影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
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DOI：
10.1073/pnas.2214988119
发表时间：
2022-12-13
影响因子：
11.1
作者：
Jung, Yoon Hee;Wang, Hsiao-Lin, V;Ruiz, Daniel;Bixler, Brianna J.;Linsenbaum, Hannah;Xiang, Jian-Feng;Forestier, Samantha;Shafik, Andrew M.;Jin, Peng;Corces, Victor G.
通讯作者：
Corces, Victor G.
影响因子：
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通讯作者：
Peters, Antoine H. F. M.
影响因子：
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作者：
Jung, Yoon Hee;Kremsky, Isaac;Corces, Victor G.
通讯作者：
Corces, Victor G.
影响因子：
8.8
作者：
Jung YH;Sauria MEG;Lyu X;Cheema MS;Ausio J;Taylor J;Corces VG
通讯作者：
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