机构地区:[1]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 [2]Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China [3]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing100191, China [4]National Institute of Biological Sciences, Beijing 102206, China [5]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China [6]Beijing Advanced Innovation Center for Genomics, Beijing 100871, China [7]peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
出 处:《Cell Research》2017年第2期165-183,共19页细胞研究(英文版)
基 金:LY, JQ and FT were supported by grants from the National Natural Science Foundation of China (31230047, 31322037, 31 522034, 31271543, 31571544 and 81521002) and the National Basic Research Program of China (2014CB943200 and 2012CB966704). JQ and FT were also supported by a grant from the Beijing Municipal Science and Technology Commission (D 151100002415000). LY was supported by a grant from the National High Technology Research and Development Program Grant (2015AA020407). The work was supported by Beijing Advanced Innovation Center for Genomics at Peking University. We thank Mr Zhonglin Fu, Ms Xuefang Zhang and Ms Shujing Wang from the National Center for Protein Sciences Beijing (Peking University) for their excellent assistance with the FACS.
摘 要: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 ceils (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.
关 键 词:CHROMATIN EPIGENETICS TRANSCRIPTION stem cell biology development
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