Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos
Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos
复制标题
植入前胚胎中 H3K4me3 和 H3K27me3 染色质结构域的独特特征。
DOI：
10.1038/nature19362
复制
发表时间：
2016-09-22
期刊：
影响因子：
64.8
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Liu, Xiaoyu;Wang, Chenfei;Gao, Shaorong
组蛋白修饰在哺乳动物胚胎发育过程中调控发育基因的表达具有关键作用。然而，植入前胚胎组蛋白修饰的全基因组分析由于所需材料的缺乏而受到阻碍。本研究采用小范围染色质免疫沉淀测序（ChIP-seq）方法，绘制了小鼠着床前胚胎中组蛋白H3赖氨酸4三甲基化（H3K4me3）和组蛋白H3赖氨酸27三甲基化（H3K27me3）的全基因组图谱，它们分别与基因激活和抑制相关。我们发现，受精后H3K4me3的重建，特别是启动子区域的重建，比H3K27me3的重建要快得多，这与双细胞阶段合子基因组激活的主要浪潮是一致的。此外，H3K4me3和H3K27me3在着床前胚胎中具有明显的序列偏好和动态特征。尽管H3K4me3修饰始终发生在转录起始位点，但H3K4me3结构域的宽度是一个高度动态的特征。值得注意的是，广泛的H3K4me3结构域（宽度大于5kb）不仅在着床前发育中具有较高的转录活性和细胞特性，而且在从内细胞群衍生出胚胎干细胞和从滋养外胚层衍生出滋养层干细胞的过程中也具有较高的转录活性和细胞特性。与胚胎干细胞相比，我们发现早期胚胎中的二价性（即H3K4me3和H3K27me3共存）相对较少且不稳定。综上所述，我们的研究结果提供了着床前胚胎中H3K4me3和H3K27me3修饰的全基因组图谱，有助于进一步探索早期胚胎的表观遗传调控机制。
Histone modifications have critical roles in regulating the expression of developmental genes during embryo development in mammals,. However, genome-wide analyses of histone modifications in pre-implantation embryos have been impeded by the scarcity of the required materials. Here, by using a small-scale chromatin immunoprecipitation followed by sequencing (ChIP–seq) method, we map the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), which are associated with gene activation and repression,, respectively, in mouse pre-implantation embryos. We find that the re-establishment of H3K4me3, especially on promoter regions, occurs much more rapidly than that of H3K27me3 following fertilization, which is consistent with the major wave of zygotic genome activation at the two-cell stage. Furthermore, H3K4me3 and H3K27me3 possess distinct features of sequence preference and dynamics in pre-implantation embryos. Although H3K4me3 modifications occur consistently at transcription start sites, the breadth of the H3K4me3 domain is a highly dynamic feature. Notably, the broad H3K4me3 domain (wider than 5 kb) is associated with higher transcription activity and cell identity not only in pre-implantation development but also in the process of deriving embryonic stem cells from the inner cell mass and trophoblast stem cells from the trophectoderm. Compared to embryonic stem cells, we found that the bivalency (that is, co-occurrence of H3K4me3 and H3K27me3) in early embryos is relatively infrequent and unstable. Taken together, our results provide a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, facilitating further exploration of the mechanism for epigenetic regulation in early embryos.