Multiple chromatin modifiers associated with H3K9me3 play important roles in the transition from embryonic stem cells to 2-cell (2C)-like cells. However, it remains elusive how H3K9me3 is remodeled and its association with totipotency. Here, we integrated transcriptome and H3K9me3 profiles to conduct a detailed comparison of 2C embryos and 2C-like cells. Globally, H3K9me3 is highly preserved and H3K9me3 dynamics within the gene locus is not associated with gene expression change during 2C-like transition. Promoter-deposited H3K9me3 plays non-repressive roles in the activation of genes during 2C-like transition. In contrast, transposable elements, residing in the nearby regions of up-regulated genes, undergo extensive elimination of H3K9me3 and are tended to be induced in 2C-like transitions. Furthermore, a large fraction of trophoblast stem cell-specific enhancers undergo loss of H3K9me3 exclusively in MERVL⁺/Zscan4⁺ cells. Our study therefore reveals the unique H3K9me3 profiles of 2C-like cells, facilitating the further exploration of totipotency.

与 H3K9me3 相关的多个染色质修饰剂在胚胎干细胞向 2 细胞 (2C) 样细胞的转变中发挥重要作用。然而，H3K9me3 的重塑方式及其与全能性的关联仍然难以捉摸。在这里，我们整合了转录组和 H3K9me3 配置文件，对 2C 胚胎和 2C 样细胞进行了详细比较。在全球范围内，H3K9me3 高度保存，基因座内的 H3K9me3 动力学与 2C 样转换期间的基因表达变化无关。启动子沉积的 H3K9me3 在 2C 样转换期间在基因激活中起着非抑制作用。相反，位于上调基因附近区域的转座因子经历 H3K9me3 的广泛消除，并且倾向于在 2C 样转换中被诱导。此外，⁺ / Zscan4 ⁺细胞。因此，我们的研究揭示了 2C 样细胞的独特 H3K9me3 配置文件，有助于进一步探索全能性。