Shao Gen-Bao, Chen Jun-Chao, Zhang Liu-Ping, Huang Pan, Lu Hong-Yan, Jin Jie, Gong Ai-Hua, Sang Jian-Rong
Department of Biology, School of Medical Science and Laboratory Medicine, Jiangsu University, 301 XueFu, Zhenjiang, 212013, China,
In Vitro Cell Dev Biol Anim. 2014 Aug;50(7):603-13. doi: 10.1007/s11626-014-9741-6. Epub 2014 Mar 12.
Extensive and dynamic chromatin remodeling occurs after fertilization, including DNA methylation and histone modifications. These changes underlie the transition from gametic to embryonic chromatin and are thought to facilitate early embryonic development. Histone H3 lysine 4 methylation (H3K4me) is an important epigenetic mechanism that associates with gene-specific activation and functions in development. However, dynamic regulation of H3K4me during early embryonic development remains unclear. Herein, the authors examined the dynamic changes of H3K4me and its key regulators (Ash1l, Ash2l, Kmt2a, Kmt2b, Kmt2c, Setd1a, Setd7, Kdm1a, Kdm1b, Kdm5a, Kdm5b, Kdm5c, and Kdm5d) in mouse oocytes and preimplantation embryos. An increase in levels of H3K4me2 and me3 was observed at the one- to two-cell stages (P < 0.05), corresponding to the period of embryonic genome activation (EGA). Subsequently, the H3K4me2 level dramatically decreased at the four-cell stage and remained at low level until the blastocyst stage (P < 0.05), whereas the H3K4me3 level transiently decreased in the four-cell embryos but steadily increased to the peak in the blastocysts (P < 0.05). The high level of H3K4me2 during the EGA was coinciding with a peak expression of its methyltransferase, ASH2L, which may stabilize this methylation level during this period. Correspondingly, a concomitant decrease in levels of its demethylases, KDM5B and KDM1A, was observed. H3K4me3 was correlated to the expression of its methyltransferase (KMT2B) and demethylase (KDM5A). Thus, these enzymes may function for the EGA and the first lineage segregation in preimplantation mouse embryos.
受精后会发生广泛而动态的染色质重塑，包括DNA甲基化和组蛋白修饰。这些变化是配子染色质向胚胎染色质转变的基础，并被认为有助于早期胚胎发育。组蛋白H3赖氨酸4甲基化（H3K4me）是一种重要的表观遗传机制，与基因特异性激活相关并在发育过程中发挥作用。然而，早期胚胎发育过程中H3K4me的动态调控仍不清楚。在此，作者研究了小鼠卵母细胞和植入前胚胎中H3K4me及其关键调节因子（Ash1l、Ash2l、Kmt2a、Kmt2b、Kmt2c、Setd1a、Setd7、Kdm1a、Kdm1b、Kdm5a、Kdm5b、Kdm5c和Kdm5d）的动态变化。在1至2细胞阶段观察到H3K4me2和me3水平增加（P < 0.05），这与胚胎基因组激活（EGA）时期相对应。随后，H3K4me2水平在4细胞阶段急剧下降并一直保持在低水平直至囊胚阶段（P < 0.05），而H3K4me3水平在4细胞胚胎中短暂下降，但在囊胚中稳步增加至峰值（P < 0.05）。EGA期间H3K4me2的高水平与其甲基转移酶ASH2L 的峰值表达一致，这可能在此期间稳定这种甲基化水平。相应地，观察到其去甲基酶KDM5B和KDM1A水平同时下降。H3K4me3与其甲基转移酶（KMT2B）和去甲基酶（KDM5A）的表达相关。因此，这些酶可能在植入前小鼠胚胎的EGA和第一次谱系分离中发挥作用。
