Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Cell Stem Cell. 2022 Jul 7;29(7):1031-1050.e12. doi: 10.1016/j.stem.2022.06.006.
Reprogramming of H3K9me3-dependent heterochromatin is required for early development. How H3K9me3 is involved in early human development remains, however, largely unclear. Here, we resolve the temporal landscape of H3K9me3 during human preimplantation development and its regulation for diverse hominoid-specific retrotransposons. At the 8-cell stage, H3K9me3 reprogramming at hominoid-specific retrotransposons termed SINE-VNTR-Alu (SVA) facilitates interaction between certain promoters and SVA-derived enhancers, promoting the zygotic genome activation. In trophectoderm, de novo H3K9me3 domains prevent pluripotent transcription factors from binding to hominoid-specific retrotransposons-derived regulatory elements for inner cell mass (ICM)-specific genes. H3K9me3 re-establishment at SVA elements in the ICM is associated with higher transcription of DNA repair genes, when compared with naive human pluripotent stem cells. Our data demonstrate that species-specific reorganization of H3K9me3-dependent heterochromatin at hominoid-specific retrotransposons plays important roles during early human development, shedding light on how the epigenetic regulation for early development has evolved in mammals.
H3K9me3 依赖性异染色质的重编程对于早期发育是必需的。然而，H3K9me3 如何参与早期人类发育在很大程度上仍不清楚。在这里，我们解决了人类胚胎植入前发育过程中 H3K9me3 的时间景观及其对不同人猿特异性反转录转座子的调控。在 8 细胞阶段，人猿特异性反转录转座子（称为 SINE-VNTR-Alu，SVA）处的 H3K9me3 重编程促进了某些启动子和 SVA 衍生增强子之间的相互作用，促进了合子基因组激活。在滋养外胚层中，从头形成的 H3K9me3 结构域阻止多能转录因子与内细胞团（ICM）特异性基因的人猿特异性反转录转座子衍生调控元件结合。与原始人类多能干细胞相比，在 ICM 中的 SVA 元件处重新建立 H3K9me3 与 DNA 修复基因的更高转录相关。我们的数据表明，人猿特异性反转录转座子处 H3K9me3 依赖性异染色质的物种特异性重排在人类早期发育中发挥重要作用，揭示了早期发育的表观遗传调控在哺乳动物中是如何进化的。
