Echs1介导的组蛋白巴豆酰化促进早期哺乳动物胚胎中的合子基因组激活和重复元件的表达。
Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos.
作者信息
Wang Yong-Feng, Wan Yu-Ting, Qi Qian-Rong, Tian Qing, Liu Xin-Mei, Xie Qing-Zhen, Yin Ying, Zhou Li-Quan
机构信息
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Center for Reproductive Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
出版信息
Nat Commun. 2025 Jul 1;16(1):5630. doi: 10.1038/s41467-025-60565-z.
Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human early embryos. Our analysis reveals that histone crotonylation is highly enriched at promoter regions and exhibits distinct dynamic patterns throughout embryogenesis. Notably, strong histone crotonylation signals are observed at the mouse 2-cell and human 4-to-8-cell stages, coinciding with zygotic genome activation. In mice, Echs1 knockdown in oocytes, which suppresses histone crotonylation, results in developmental arrest at the 2-cell stage. Further investigation demonstrates that reduced histone crotonylation impairs transcriptional activity at zygotic genome activation genes, retrotransposon elements, and ribosomal DNA loci. Moreover, early embryos from aged female mice exhibit significantly diminished histone crotonylation, while supplementation with exogenous sodium crotonate enhances blastocyst formation. Collectively, our findings establish histone crotonylation as a key regulatory mechanism in early mammalian embryogenesis by facilitating transcriptional activation of zygotic genome activation genes and repetitive elements.
组蛋白巴豆酰化是一种保守的翻译后组蛋白修饰,在转录调控中起关键作用。然而,其在早期胚胎发育中的功能在很大程度上仍未被探索。在此,我们对小鼠和人类早期胚胎中的组蛋白巴豆酰化进行全基因组定位。我们的分析表明,组蛋白巴豆酰化在启动子区域高度富集,并在整个胚胎发生过程中呈现出不同的动态模式。值得注意的是,在小鼠2细胞期和人类4至8细胞期观察到强烈的组蛋白巴豆酰化信号,这与合子基因组激活相吻合。在小鼠中,卵母细胞中Echs1基因敲低会抑制组蛋白巴豆酰化,导致在2细胞期发育停滞。进一步研究表明,组蛋白巴豆酰化减少会损害合子基因组激活基因、逆转座子元件和核糖体DNA位点的转录活性。此外,老年雌性小鼠的早期胚胎组蛋白巴豆酰化显著减少,而补充外源性巴豆酸钠可增强囊胚形成。总的来说,我们的研究结果通过促进合子基因组激活基因和重复元件的转录激活,将组蛋白巴豆酰化确立为早期哺乳动物胚胎发生中的一种关键调控机制。