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.

早期发育需要重编程 H3K9me3 依赖性异染色质。然而，H3K9me3 如何参与早期人类发育仍不清楚。在这里，我们解决了人类植入前发育过程中 H3K9me3 的时间景观及其对各种类人猿特异性反转录转座子的调节。在 8 细胞阶段，H3K9me3 在名为 SINE-VNTR-Alu (SVA) 的类人猿特异性反转录转座子上重编程促进某些启动子和 SVA 衍生的增强子之间的相互作用，从而促进合子基因组的激活。在滋养外胚层，从头H3K9me3 结构域可防止多能转录因子与类人猿特异性逆转录转座子衍生的内细胞团 (ICM) 特异性基因的调节元件结合。与幼稚人类多能干细胞相比，ICM 中 SVA 元件的 H3K9me3 重建与 DNA 修复基因的更高转录有关。我们的数据表明，H3K9me3 依赖性异染色质在类人猿特异性反转录转座子上的物种特异性重组在人类早期发育过程中发挥着重要作用，揭示了哺乳动物早期发育的表观遗传调控是如何进化的。