【原】H3K4me3 and H3K27me3 in pre-implantation embryos

Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos.

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|核心内容：

组蛋白修饰在哺乳动物胚胎发育过程中对发育基因的表达起着重要的调控作用。

然而，组蛋白修饰在植入前胚胎的全基因组分析一直受到缺乏所需材料的阻碍。

在这里，通过使用小规模的染色质免疫沉淀基因组测序(ChIP-seq)方法，我们绘制了组蛋白 h 3赖氨酸4三甲基化(H3K4me3)和组蛋白 h 3赖氨酸27三甲基化(H3K27me3)的全基因组图谱，它们分别与小鼠着床前胚胎的基因激活和抑制有关。

我们发现 H3K4me3在受精后的重建速度远远快于 H3K27me3，特别是在启动子区，这与双细胞阶段合子基因组激活的主要波动相一致。

此外，H3K4me3和 H3K27me3在植入前胚胎中具有明显的序列偏好和动态特征。

虽然 H3K4me3的修饰在转录起始位点一致，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)不仅在胚胎植入前的发育过程中，而且在胚胎干细胞来源于内细胞团和滋养层干细胞来源于滋养层的过程中，都与较高的转录活性和细胞特性有关。

与胚胎干细胞相比，H3K4me3和 H3K27me3在早期胚胎中同时出现的双价现象相对少见，且不稳定。

总之，我们的结果提供了一个全基因组图谱的 H3K4me3和 H3K27me3修饰在植入前胚胎，促进了表观遗传调控机制在早期胚胎的进一步探索。

Figure 1 | Dynamics of the histone modification landscape in early mouse embryos.  a, Schematic for the pre-implantation embryos and cell line samples used in ULINChIP analysis.  b, Alluvial plots (left panel) showing the global dynamics of H3K4me3- only and H3K27me3-only regions during early embryo development. Each line represents a 200-bp bin defined on the ChromHMM categories, and the total regions are those classified as this state in at least one analysed stage. The global dynamics (solid line) and chromosome X dynamics (dashed line) were plotted separately (right panel).  c, Genome browser view of the H3K4me3 density in the Copb and Actb range and the H3K27me3 density at the Hoxc region in pre-implantation embryos. The ChIP–seq RPM (reads per million mapped reads) was smoothed based on the mean of 5 pixels using the UCSC genome browser.

原文摘要：

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.

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参考文献：https:///10.1038/nature19362

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