title: Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming.
abstract: The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.
authors.affiliation: College of Life Science, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences (NIBS), Beijing 102206, China; Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Kou
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: czjiang@tongji.edu.cn.
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: gaoshaorong@tongji.edu.cn.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002459:Cell Fusion; D065150:Cellular Reprogramming; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014162:Transfection; D019076:Transgenes
chemical_list: D006657:Histones; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse
keywords: Oct4; histone modification; iPSC; reprogramming