Changes in H3K79 methylation during preimplantation development in mice

Changes in H3K79 methylation during preimplantation development in mice
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DOI:
10.1095/biolreprod.107.063453
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发表时间:
2008-03-01
影响因子:
3.6
通讯作者:
Aoki, Fugaku
Aoki, Fugaku
中科院分区:
生物学2区
文献类型:
--
作者:
Ooga, Masatoshi;Inoue, Azusa;Aoki, Fugaku

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在受精前后,分化的卵母细胞的基因表达模式被重新编程为全能植入前胚胎的基因表达模式。为了阐明基因组重编程的机制,我们用免疫细胞化学方法研究了组蛋白H3赖氨酸79二甲基化(H3K79me2)和三甲基化(H3K79me3)在卵母细胞和植入前胚胎中的表达。在体细胞和卵母细胞中,H3K79me2分布在整个基因组中,而H3K79me3定位在着丝粒周围的异染色质区域,其中没有活性基因。由于H3K79me2被认为是一个活跃的基因标记,H3K79甲基化似乎具有不同的功能,这取决于在相同残基上添加的甲基的数量。受精后不久,H3K79me2和H3K79me3均下降,除有丝分裂(M期)H3K79me2短暂升高外,间期(囊胚期前)均维持低甲基化状态。H3K79me3在植入前一直未检测到,即使在M期也未检测到H3K79me3。为了研究H3K79me2在基因组重编程中的作用,将体细胞核移植到去核的卵母细胞中。孤雌激活后,这些细胞核中的H3K79me2去甲基化。然而,激活后7h移植到孤雌胚胎中的核没有去甲基化。这表明受精后H3K79甲基化的消除与基因组重编程有关。
The gene expression pattern of differentiated oocytes is reprogrammed into that of totipotent preimplantation embryos before and/or after fertilization. To elucidate the mechanisms of genome reprogramming, we investigated histone H3 lysine 79 dimethylation (H3K79me2) and trimethylation (H3K79me3) in oocytes and preimplantation embryos via immunocytochemistry. In somatic cells and oocytes, H3K79me2 was observed throughout the genome, whereas H3K79me3 was localized in the pericentromeric heterochromatin regions in which there are no active genes. Because H3K79me2 is considered an active gene marker, H3K79 methylation seems to have differing functions depending on the number of methyl groups added on the same residues. Both H3K79me2 and H3K79me3 decreased soon after fertilization, and the hypomethylated state was maintained at interphase (before the blastocyst stage), except for a transient increase in H3K79me2 at mitosis (M phase). H3K79me3 was not detected throughout preimplantation, even at M phase. To investigate the involvement of H3K79me2 in genome reprogramming, somatic nuclei were transplanted into enucleated oocytes. H3K79me2 in these nuclei was demethylated following parthenogenetic activation. However, the nuclei that had been transplanted into the parthenogenetic embryos 7 h after activation were not demethylated. This suggests that the elimination of H3K79 methylation after fertilization is involved in genomic reprogramming.