Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Biochem Biophys Res Commun. 2020 Feb 5;522(2):422-427. doi: 10.1016/j.bbrc.2019.11.114. Epub 2019 Nov 22.
During development, fertilization triggers totipotency establishment, featured by zygotic genome activation/embryonic genome activation (ZGA/EGA). Mouse embryonic stem cells (mESCs) occasionally cycle through a two-cell (2C)-like status with activated expression of Dux and its targeted ZGA genes. Here, we demonstrate that deficiency of histone variant H3.3 dramatically stimulates expression of ZGA genes in mESCs. Our analysis revealed that H3.3 directly associates with Dux locus and inhibits Dux expression, therefore it is an important upstream regulator of Dux. Our finding is further supported by transcriptome change in early mouse embryos with H3.3 knockdown. We suggest that proper H3.3 level in early embryos is important to orchestrate ZGA activity for totipotency establishment.
在发育过程中，受精触发全能性的建立，其特征是合子基因组激活/胚胎基因组激活（ZGA/EGA）。小鼠胚胎干细胞（mESCs）偶尔会经历一个具有激活的 Dux 及其靶向 ZGA 基因表达的二细胞（2C）样状态。在这里，我们证明组蛋白变体 H3.3 的缺乏会显著刺激 mESCs 中 ZGA 基因的表达。我们的分析表明，H3.3 直接与 Dux 基因座结合并抑制 Dux 的表达，因此它是 Dux 的一个重要上游调节因子。我们的发现进一步得到了 H3.3 敲低的早期小鼠胚胎转录组变化的支持。我们认为，早期胚胎中适当的 H3.3 水平对于协调 ZGA 活性以建立全能性是很重要的。
