Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development
Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development
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DOI：
10.15252/embr.201439700
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发表时间：
2015-07-01
期刊：
影响因子：
7.7
通讯作者：
Okada, Yuki
中科院分区：
文献类型：
--
作者：
Aoshima, Keisuke;Inoue, Erina;Okada, Yuki
表观遗传修饰，如DNA甲基化和组蛋白修饰，在受精后不久主要在父本原核中动态改变。为了确定哪些组蛋白修饰是早期胚胎发育所需的，我们利用了组蛋白K-M突变体，其阻止了突变位点处的内源性组蛋白甲基化。我们制备了组蛋白H3.3、K4 M、K9 M、K27 M和K36 M的四种单一K-M突变体，并证明了受精前胚胎中H3.3 K4 M的过表达导致发育停滞，而受精后的过表达不影响发育。此外，H3 K4甲基化的丧失主要在父本原核中降低了次要合子基因激活（ZGA）的水平，并且我们从H3 K4甲基转移酶Mll 3/4的敲低中获得了类似的结果。因此，我们得出结论，H3 K4甲基化，可能建立M113/4在早期原核阶段，是必不可少的小ZGA在父亲的原核，这是必要的后续植入前小鼠的发展。
Epigenetic modifications, such as DNA methylation and histone modifications, are dynamically altered predominantly in paternal pronuclei soon after fertilization. To identify which histone modifications are required for early embryonic development, we utilized histone K-M mutants, which prevent endogenous histone methylation at the mutated site. We prepared four single K-M mutants for histone H3.3, K4M, K9M, K27M, and K36M, and demonstrate that overexpression of H3.3 K4M in embryos before fertilization results in developmental arrest, whereas overexpression after fertilization does not affect the development. Furthermore, loss of H3K4 methylation decreases the level of minor zygotic gene activation (ZGA) predominantly in the paternal pronucleus, and we obtained similar results from knockdown of the H3K4 methyltransferase Mll3/4. We therefore conclude that H3K4 methylation, likely established by Mll3/4 at the early pronuclear stage, is essential for the onset of minor ZGA in the paternal pronucleus, which is necessary for subsequent preimplantation development in mice.