日前，同济大学高绍荣实验室在《Nature》杂志在线发表题为 “Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos” 的文章。首次从全基因组水平上揭示了胚胎发育过程中，组蛋白H3K4me3和HK27me3修饰建立过程差异，并发现宽的（broad）H3K4me3修饰在植入前胚胎发育过程中对基因表达调控发挥重要作用。
组蛋白修饰在哺乳动物胚胎发育期间对发育基因的表达调控起着关键作用。然而，对植入前胚胎的组蛋白修饰的全基因组分析由于所需材料的缺乏而受限制。该实验室通过使用一个小规模的染色质免疫和ChIP-seq方法，在小鼠植入前胚胎中确立了H3K4me3和H3K27me3的全基因组图谱，这两个基因分别与基因的激活和抑制相关。他们发现，受精后H3K4me3的重建，尤其是在启动子区域，比H3K27me3快得多，这符合2细胞胚胎阶段中合子基因组激活的情况。
此外，植入前胚胎中H3K4me3和H3K27me3具有明显的序列偏好和动力学差异。通过分析检测到的数据，他们发现组蛋白H3K4me3和H3K27me3修饰的建立规律明显不同，H3K4me3修饰的建立更迅速，并且倾向于建立在CpG含量较高且DNA甲基化水平较低的启动子区域，而H3K27me3修饰的建立比较缓慢，并且倾向于建立在CpG含量较低的启动子区域。研究还发现，在胚胎发育过程中，H3K4me3修饰的宽度是逐步变化的，很少出现宽的H3K4me3修饰直接的建立和去除，这使宽的H3K4me3修饰可以维持相对稳定。总之，该研究成果第一次建立起了小鼠植入前胚胎发育过程中的组蛋白H3K4me3和H3K27me3修饰图谱，并发现了植入前胚胎发育特殊的表观遗传调控机制。
原文摘要：
Histone modifications have critical roles in regulating the expression of developmental genes during embryo development in mammals1, 2. 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) method3, 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 repression4, 5, 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.
原文链接
http://www.nature.com/nature/journal/v537/n7621/pdf/nature19362.pdf
