DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells.
DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells.
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小鼠和人类胎儿生殖细胞的 DNA 甲基化和染色质可及性分析
DOI：
10.1038/cr.2016.128
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发表时间：
2017-02
期刊：
影响因子：
44.1
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Guo H;Hu B;Yan L;Yong J;Wu Y;Gao Y;Guo F;Hou Y;Fan X;Dong J;Wang X;Zhu X;Yan J;Wei Y;Jin H;Zhang W;Wen L;Tang F;Qiao J
染色质重塑对于人类原始生殖细胞的表观遗传重编程非常重要。然而，尚未对人类胎儿生殖细胞 (FGC) 的全面染色质状态进行分析。在这里，我们使用核小体占据和甲基化测序方法来分析人类和小鼠胎儿生殖细胞发育过程中一系列关键时间点的全基因组染色质可及性和 DNA 甲基化组。我们在人和小鼠 FGC 中发现了 116 887 和 137 557 个核小体耗尽区 (NDR)，涵盖了大量种系特异性和高度动态的调控基因组元件，例如增强子。此外，我们发现远端NDR特异性富集于人类FGC中多能性和生殖细胞主调节因子（例如NANOG、SOX17、AP2γ和OCT4）的结合基序，表明人类FGC中多能性相关基因和生殖细胞特异性基因之间存在微妙的调节平衡，以及这些基因对于体内生殖细胞发育的功能意义。我们的工作为剖析人类和小鼠 FGC 表观基因组重编程过程中的染色质状态转变动态提供了全面且高分辨率的路线图。
Chromatin remodeling is important for the epigenetic reprogramming of human primordial germ cells. However, the comprehensive chromatin state has not yet been analyzed for human fetal germ cells (FGCs). Here we use nucleosome occupancy and methylation sequencing method to analyze both the genome-wide chromatin accessibility and DNA methylome at a series of crucial time points during fetal germ cell development in both human and mouse. We find 116 887 and 137 557 nucleosome-depleted regions (NDRs) in human and mouse FGCs, covering a large set of germline-specific and highly dynamic regulatory genomic elements, such as enhancers. Moreover, we find that the distal NDRs are enriched specifically for binding motifs of the pluripotency and germ cell master regulators such as NANOG, SOX17, AP2γ and OCT4 in human FGCs, indicating the existence of a delicate regulatory balance between pluripotency-related genes and germ cell-specific genes in human FGCs, and the functional significance of these genes for germ cell development in vivo. Our work offers a comprehensive and high-resolution roadmap for dissecting chromatin state transition dynamics during the epigenomic reprogramming of human and mouse FGCs.