Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Nat Cell Biol. 2018 May;20(5):620-631. doi: 10.1038/s41556-018-0093-4. Epub 2018 Apr 23.
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 that Chaf1a is 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.
H3K9me3 依赖性异染色质是细胞命运改变的主要障碍，在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图谱。我们发现 H3K9me3 在启动子和长末端重复序列（LTRs）中表现出不同的动态特征。受精后，双亲基因组都经历了大规模的 H3K9me3 重建，并且亲本 H3K9me3 信号的不平衡一直持续到囊胚期。LTR 上 H3K9me3 的重建涉及沉默它们由 DNA 去甲基化触发的活性转录。我们发现 Chaf1a 对于 LTR 上 H3K9me3 的建立以及随后的转录抑制是必不可少的。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 依赖性异染色质在早期胚胎发育过程中经历了剧烈的重编程，并为进一步探索早期胚胎中的表观遗传机制提供了有价值的资源。
