清华大学颉伟课题组利用原肠运动的表观基因组分析揭示了活化多能性的独特染色质状态。相关论文2019年12月16日发表于国际学术期刊《自然—遗传学》上。

研究人员表示，着床后，上胚层（Epi）从初始过渡到活化的多能性，然后产生了三个胚层。在这个发育窗口期间如何重新塑造染色质仍然知之甚少。

在此期间，研究人员对染色质景观进行了全基因组研究。研究人员发现外胚层中的增强子已经在胚胎第6.5天（E6.5）Epi进入活化的多能状态时就已经预可及。出乎意料的是，组蛋白H3在赖氨酸4（H3K4me3）处的强三甲基化作用出现在E6.5 Epi的发育基因启动子上，并与H3K27me3正相关，从而建立了双价性。这些基因还显示出增强的空间相互作用。在着床前的胚胎中实际上不存在强的双价性和空间聚类，并且在命运决定的世系中明显减少。最后，研究人员表明KMT2B对于在E6.5处建立二价H3K4me3是必不可少的，但稍后将一定程度上可有可无。它的缺乏导致发育基因的激活受损和随后的胚胎致死性。因此，这些数据表征了谱系特异性染色质重塑以及活化多能性的独特染色质状态。

附：英文原文

Title: Epigenomic analysis of gastrulation identifies a unique chromatin state for primed pluripotency

Author: Yunlong Xiang, Yu Zhang, Qianhua Xu, Chen Zhou, Bofeng Liu, Zhenhai Du, Ke Zhang, Bingjie Zhang, Xiaoxiao Wang, Srimonta Gayen, Ling Liu, Yao Wang, Yuanyuan Li, Qiujun Wang, Sundeep Kalantry, Lei Li, Wei Xie

Issue&Volume: 2019-12-16

Abstract: Around implantation, the epiblast (Epi) transits from nave to primed pluripotency, before giving rise to the three germ layers. How chromatin is reconfigured during this developmental window remains poorly understood. We performed a genome-wide investigation of chromatin landscapes during this period. We find that enhancers in ectoderm are already pre-accessible in embryonic day 6.5 (E6.5) Epi when cells enter a primed pluripotent state. Unexpectedly, strong trimethylation of histone H3 at lysine 4 (H3K4me3) emerges at developmental gene promoters in E6.5 Epi and positively correlates with H3K27me3, thus establishing bivalency. These genes also show enhanced spatial interactions. Both the strong bivalency and spatial clustering are virtually absent in preimplantation embryos and are markedly reduced in fate-committed lineages. Finally, we show that KMT2B is essential for establishing bivalent H3K4me3 at E6.5 but becomes partially dispensable later. Its deficiency leads to impaired activation of developmental genes and subsequent embryonic lethality. Thus, our data characterize lineage-specific chromatin reconfiguration and a unique chromatin state for primed pluripotency.

DOI: 10.1038/s41588-019-0545-1

Source: https://www.nature.com/articles/s41588-019-0545-1