Nevoral Jan, Drutovic David, Vaskovicova Michaela, Benc Michal, Liska Frantisek, Valentova Iveta, Stachovicova Sara, Kubovciak Jan, Havrankova Jirina, Shavit Miki, Monsef Ladan, Iniesta-Cuerda Maria, Zalmanova Tereza, Hosek Petr, Strejcek Frantisek, Kralickova Milena, Petr Jaroslav
Faculty of Medicine in Pilsen, Biomedical Center, Charles University, Alej Svobody 76, 323 00, Pilsen, Czech Republic.
Faculty of Medicine in Pilsen, Department of Histology and Embryology, Charles University, Alej Svobody 76, 323 00, Pilsen, Czech Republic.
Sci Rep. 2024 Sep 16;14(1):21598. doi: 10.1038/s41598-024-72595-6.
Dynamic changes in maternal‒zygotic transition (MZT) require complex regulation of zygote formation, maternal transcript decay, embryonic genome activation (EGA), and cell cycle progression. Although these changes are well described, some key regulatory factors are still elusive. Sirtuin-1 (SIRT1), an NAD-dependent histone deacetylase, is a versatile driver of MZT via its epigenetic and nonepigenetic substrates. This study focused on the dynamics of SIRT1 in early embryos and its contribution to MZT. A conditional SIRT1-deficient knockout mouse model was used, accompanied by porcine and human embryos. Embryos across mammalian species showed the prominent localization of SIRT1 in the nucleus throughout early embryonic development. Accordingly, SIRT1 interacts with histone H4 on lysine K16 (H4K16) in both mouse and human blastocysts. While maternal SIRT1 is dispensable for MZT, at least one allele of embryonic Sirt1 is required for early embryonic development around the time of EGA. This role of SIRT1 is surprisingly mediated via a transcription-independent mode of action.
母源-合子转变（MZT）中的动态变化需要对合子形成、母源转录本降解、胚胎基因组激活（EGA）和细胞周期进程进行复杂调控。尽管这些变化已有详尽描述，但一些关键调控因子仍不明确。沉默调节蛋白1（SIRT1）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD）的组蛋白去乙酰化酶，通过其表观遗传和非表观遗传底物成为MZT的多功能驱动因子。本研究聚焦于早期胚胎中SIRT1的动态变化及其对MZT的作用。使用了条件性SIRT1缺陷敲除小鼠模型，并结合猪和人类胚胎进行研究。跨哺乳动物物种的胚胎在整个早期胚胎发育过程中均显示SIRT1在细胞核中显著定位。相应地，在小鼠和人类囊胚中，SIRT1与赖氨酸K16（H4K16）位点的组蛋白H4相互作用。虽然母源SIRT1对于MZT并非必需，但在EGA前后的早期胚胎发育阶段，胚胎Sirt1至少有一个等位基因是必需的。SIRT1的这一作用令人惊讶地是通过一种不依赖转录的作用模式介导的。
