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Cell Res. 2017 Feb;27(2):165-183. doi: 10.1038/cr.2016.128. Epub 2016 Nov 8.

DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells.

Guo H1, Hu B1, Yan L1,2,3, Yong J1,2,3, Wu Y4, Gao Y1, Guo F1, Hou Y1, Fan X1, Dong J1, Wang X1,2,3, Zhu X1,2,3, Yan J1,2,3, Wei Y1,2,3, Jin H1,2,3, Zhang W1,2,3, Wen L1,5, Tang F1,5,6,7, Qiao J1,2,3,7.

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Department of Obstetrics and Gynecology Third Hospital, Biomedical Institute for Pioneering Investigation via Convergence & Center for Reproductive Medicine, College of Life Sciences, Peking University, Beijing 100871, China.
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China.
National Institute of Biological Sciences, Beijing 102206, China.
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
Beijing Advanced Innovation Center for Genomics, Beijing 100871, China.
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.


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.

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