Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa

Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa
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DOI:
10.1038/nsmb.1821
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发表时间:
2010-06-01
影响因子:
16.8
通讯作者:
Peters, Antoine H. F. M.
Peters, Antoine H. F. M.
中科院分区:
生物学1区
文献类型:
--
作者:
Brykczynska, Urszula;Hisano, Mizue;Peters, Antoine H. F. M.

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在较高的真核生物中,组蛋白甲基化参与了在体细胞发育过程中维持细胞身份。由于大多数核小体在精子发生过程中被精蛋白取代,因此尚不清楚组蛋白修饰是否在表观遗传信息的父亲传播中起作用。在这里,我们表明,对三杆菌和多孔介导的基因调节重要的两种修饰在人类精子中的调节区域具有甲基化特异性分布。组蛋白H3 Lys4二甲基化(H3K4ME2)标志着与精子发生和细胞稳态相关的基因。相反,组蛋白H3 Lys27三甲基化(H3K27ME3)标志着精子中的发育调节剂,如体细胞中。但是,核小体仅在人类精子的调节区域中适度保留。但是,特别是在男配子发生或植入前胚胎中,尤其是转录起始位点周围具有广泛H3K27me3覆盖率的基因。直系同源基因的启动子在小鼠精子中类似地修饰。这些数据与PolyComb在抑制世代相传的体细胞决定因素中的作用兼容,可能会以各种方式。
In higher eukaryotes, histone methylation is involved in maintaining cellular identity during somatic development. As most nucleosomes are replaced by protamines during spermatogenesis, it is unclear whether histone modifications function in paternal transmission of epigenetic information. Here we show that two modifications important for Trithorax-and Polycomb-mediated gene regulation have methylation-specific distributions at regulatory regions in human spermatozoa. Histone H3 Lys4 dimethylation (H3K4me2) marks genes that are relevant in spermatogenesis and cellular homeostasis. In contrast, histone H3 Lys27 trimethylation (H3K27me3) marks developmental regulators in sperm, as in somatic cells. However, nucleosomes are only moderately retained at regulatory regions in human sperm. Nonetheless, genes with extensive H3K27me3 coverage around transcriptional start sites in particular tend not to be expressed during male and female gametogenesis or in preimplantation embryos. Promoters of orthologous genes are similarly modified in mouse spermatozoa. These data are compatible with a role for Polycomb in repressing somatic determinants across generations, potentially in a variegating manner.