Fukushima Hiroto S, Takeda Hiroyuki
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Nat Commun. 2025 Jun 16;16(1):5222. doi: 10.1038/s41467-025-60246-x.
Zygotic genome activation (ZGA) is a critical developmental milestone characterized by the rapid and simultaneous activation of genome-widely silenced chromatin. Various active histone modifications accumulate upon ZGA and have long been implicated in ZGA. However, their biological relevance still remains unclear. Here, we comprehensively examined the functional significance of active histone modifications and their writers during ZGA in teleost embryos. Our data propose that developmental genes and housekeeping genes are distinctively regulated during ZGA; CBP/P300 activity is required for developmental gene activation, whereas housekeeping genes depend on non-CBP/P300 histone acetylations H3K9ac/H4K16ac/H3K14ac. Moreover, accumulation of H3K4me2/3 is not prerequisite for activation of all types of genes during ZGA, in contrast to previous reports with cell lines. Finally, temporal accumulation of H3.3S31ph greatly enhances CBP/P300 activity specifically at ZGA, ensuring the activation of developmental genes. Our data demonstrate that multiple histone modifications cooperatively shape ZGA-specific gene activation programs in non-mammalian vertebrates.
合子基因组激活（ZGA）是一个关键的发育里程碑，其特征是全基因组范围内沉默的染色质迅速且同时被激活。在ZGA过程中，各种活性组蛋白修饰会积累，并且长期以来一直被认为与ZGA有关。然而，它们的生物学相关性仍不清楚。在这里，我们全面研究了硬骨鱼胚胎ZGA过程中活性组蛋白修饰及其写入酶的功能意义。我们的数据表明，在ZGA过程中，发育基因和管家基因受到不同的调控；发育基因的激活需要CBP/P300活性，而管家基因则依赖于非CBP/P300组蛋白乙酰化修饰H3K9ac/H4K16ac/H3K14ac。此外，与之前细胞系的报道相反，H3K4me2/3的积累并非ZGA过程中所有类型基因激活的先决条件。最后，H3.3S31ph的瞬时积累极大地增强了ZGA特异性的CBP/P300活性，确保了发育基因的激活。我们的数据表明，多种组蛋白修饰协同塑造了非哺乳动物脊椎动物中ZGA特异性的基因激活程序。
