Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY, 12144, USA.
Sci Rep. 2024 Feb 24;14(1):4505. doi: 10.1038/s41598-024-55189-0.
The placenta serves as an essential organ for fetal growth throughout pregnancy. Histone modification is a crucial regulatory mechanism involved in numerous biological processes and development. Nevertheless, there remains a significant gap in our understanding regarding the epigenetic regulations that influence trophoblast lineage differentiation, a fundamental aspect of placental development. Here, through comprehensive mapping of H3K4me3, H3K27me3, H3K9me3, and H3K27ac loci during the differentiation of trophoblast stem cells (TSCs) into syncytiotrophoblasts (STs) and extravillous trophoblasts (EVTs), we reveal dynamic reconfiguration in H3K4me3 and H3K27ac patterns that establish an epigenetic landscape conducive to proper trophoblast lineage differentiation. We observe that broad H3K4me3 domains are associated with trophoblast lineage-specific gene expression. Unlike embryonic stem cells, TSCs lack robust bivalent domains. Notably, the repression of ST- and EVT-active genes in TSCs is primarily attributed to the weak H3K4me3 signal rather than bivalent domains. We also unveil the inactivation of TSC enhancers precedes the activation of ST enhancers during ST formation. Our results provide a comprehensive global map of diverse histone modifications, elucidating the dynamic histone modifications during trophoblast lineage differentiation.
胎盘是妊娠期间胎儿生长所必需的器官。组蛋白修饰是参与许多生物过程和发育的关键调节机制。然而，我们对于影响滋养层谱系分化的表观遗传调控的理解仍然存在很大的差距，而滋养层谱系分化是胎盘发育的一个基本方面。在这里，我们通过对滋养层干细胞（TSCs）向合体滋养层（ST）和绒毛外滋养层（EVT）分化过程中 H3K4me3、H3K27me3、H3K9me3 和 H3K27ac 位点的全面作图，揭示了 H3K4me3 和 H3K27ac 模式的动态重排，这些模式建立了有利于适当的滋养层谱系分化的表观遗传景观。我们观察到广泛的 H3K4me3 结构域与滋养层谱系特异性基因表达相关。与胚胎干细胞不同，TSCs 缺乏稳健的双价结构域。值得注意的是，TSCs 中 ST 和 EVT 活性基因的抑制主要归因于 H3K4me3 信号较弱，而不是双价结构域。我们还揭示了在 ST 形成过程中，TSC 增强子的失活先于 ST 增强子的激活。我们的研究结果提供了多样化组蛋白修饰的全面全局图谱，阐明了滋养层谱系分化过程中的动态组蛋白修饰。
