Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection.-猫眼课题宝

DOI：

10.1016/j.celrep.2019.03.002

发表时间：

2019-04

期刊：

Cell reports

影响因子：

8.8

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Wan Kin Au Yeung;Julie Brind’Amour;Yu Hatano;K. Yamagata;R. Feil;M. Lorincz;M. Tachibana;Y. Shinkai;H. Sasaki

哺乳动物组蛋白甲基转移酶G9a(也称为EHMT2)在染色质上沉积H3K9me2，是种植后发育所必需的。然而，它在卵子发生和着床前发育中的作用仍然知之甚少。我们发现，在小鼠卵母细胞中，H3K9me2富含染色质结构域的CG甲基化通常是缺失的，与它们在胚胎干细胞和体细胞中的关联形成对比。卵母细胞特异性的G9a中断导致H3K9me2的浓缩减少，并损害了卵母细胞中异染色质的重组，但仅检测到轻微的CG甲基化减少。此外，在卵母细胞和2-细胞胚胎中，G9a缺失对基因和反转录转座子的表达影响有限。尽管这些卵母细胞的CG甲基化受到的影响很小，但来自这些卵母细胞的植入前胚胎表现出异常的染色体分离和频繁的发育停滞。我们的发现阐明了G9a在植入前发育中独立于CG甲基化的功能重要性，并对H3K9me2在受精卵CG甲基化保护中的作用提出了质疑。

Mammalian histone methyltransferase G9a (also called EHMT2) deposits H3K9me2 on chromatin and is essential for postimplantation development. However, its role in oogenesis and preimplantation development remains poorly understood. We show that H3K9me2-enriched chromatin domains in mouse oocytes are generally depleted of CG methylation, contrasting with their association in embryonic stem and somatic cells. Oocyte-specific disruption ofG9aresults in reduced H3K9me2 enrichment and impaired reorganization of heterochromatin in oocytes, but only a modest reduction in CG methylation is detected. Furthermore, in both oocytes and 2-cell embryos, G9a depletion has limited impact on the expression of genes and retrotransposons. Although their CG methylation is minimally affected, preimplantation embryos derived from such oocytes show abnormal chromosome segregation and frequent developmental arrest. Our findings illuminate the functional importance of G9a independent of CG methylation in preimplantation development and call into question the proposed role for H3K9me2 in CG methylation protection in zygotes.

Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection.

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