Reprogramming of H3K9me3-dependent heterochromatin during mammalian embryo development
Reprogramming of H3K9me3-dependent heterochromatin during mammalian embryo development
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哺乳动物胚胎发育过程中 H3K9me3 依赖性异染色质的重编程
DOI：
10.1038/s41556-018-0093-4
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发表时间：
2018-05-01
影响因子：
21.3
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Wang, Chenfei;Liu, Xiaoyu;Gao, Shaorong
H3 K9 me3依赖性异染色质是细胞命运变化的主要障碍，受精后必须重新编程。然而，这些事件的分子细节在早期胚胎中缺乏。在这里，我们绘制了小鼠早期胚胎中H3K9me3修饰的全基因组分布。我们发现H3K9me3在启动子和长末端重复序列（LTRs）中表现出明显的动态特征。两个亲本基因组在受精后都经历大规模的H3K9me3重建，并且亲本H3K9me3信号的不平衡持续到胚泡。H3K9me3在LTR上的重建参与了由DNA去甲基化触发的LTR活性转录的沉默。我们确定Chaf1是在LTR上建立H3K9me3和随后的转录抑制所必需的。最后，我们发现谱系特异性H3K9me3在植入后胚胎中建立。总之，我们的数据表明，H3K9me3依赖的异染色质在早期胚胎发育过程中经历了戏剧性的重编程，并为进一步探索早期胚胎的表观遗传机制提供了宝贵的资源。
H3K9me3-dependent heterochromatin is a major barrier of cell fate changes that must be reprogrammed after fertilization. However, the molecular details of these events are lacking in early embryos. Here, we map the genome-wide distribution of H3K9me3 modifications in mouse early embryos. We find that H3K9me3 exhibits distinct dynamic features in promoters and long terminal repeats (LTRs). Both parental genomes undergo large-scale H3K9me3 reestablishment after fertilization, and the imbalance in parental H3K9me3 signals lasts until blastocyst. The rebuilding of H3K9me3 on LTRs is involved in silencing their active transcription triggered by DNA demethylation. We identify thatChaf1ais essential for the establishment of H3K9me3 on LTRs and subsequent transcriptional repression. Finally, we find that lineage-specific H3K9me3 is established in post-implantation embryos. In summary, our data demonstrate that H3K9me3-dependent heterochromatin undergoes dramatic reprogramming during early embryonic development and provide valuable resources for further exploration of the epigenetic mechanism in early embryos.