An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos
An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos
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DOI：
10.1038/s41467-018-08244-0
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发表时间：
2019-01-21
影响因子：
16.6
通讯作者：
Li, Ge
中科院分区：
文献类型：
--
作者：
Liu, Longqi;Leng, Lizhi;Li, Ge
人类植入前胚胎发育涉及染色质结构和转录活性的广泛变化。在这里，我们报告了LiCAT-seq技术，该技术能够在超低细胞输入的情况下同时分析染色质可及性和基因表达，并绘制人类植入前胚胎的染色质可及性和转录组景观。我们观察到精子和胚胎各阶段之间的染色质可及性的总体差异，发现精子中的可及区域往往发生在基因贫乏的基因组区域。两个数据集之间的综合分析揭示了可接近的染色质的建立与胚胎基因组激活（EGA）之间的强关联，并揭示了EGA特异性的转录因子和内源性逆转录病毒（ERVs）。特别是，大部分早期激活的基因和ERV被DUX 4结合，并且早在2-至4-细胞阶段就变得可接近。因此，我们的研究结果提供了人类胚胎植入前发育所固有的分子事件的机制见解。
Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here, we report on LiCAT-seq, a technique that enables simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells, and map the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions. Integrative analyses between the two datasets reveals strong association between the establishment of accessible chromatin and embryonic genome activation (EGA), and uncovers transcription factors and endogenous retrovirus (ERVs) specific to EGA. In particular, a large proportion of the early activated genes and ERVs are bound by DUX4 and become accessible as early as the 2- to 4-cell stages. Our results thus offer mechanistic insights into the molecular events inherent to human pre-implantation development.