title: Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells.
abstract: Nucleosome positioning and histone modification play a critical role in gene regulation, but their role during reprogramming has not been fully elucidated. Here, we determined the genome-wide nucleosome coverage and histone methylation occupancy in mouse embryonic fibroblasts (MEFs), induced pluripotent stem cells (iPSCs) and pre-iPSCs. We found that nucleosome occupancy increases in promoter regions and decreases in intergenic regions in pre-iPSCs, then recovers to an intermediate level in iPSCs. We also found that nucleosomes in pre-iPSCs are much more phased than those in MEFs and iPSCs. During reprogramming, nucleosome reorganization and histone methylation around transcription start sites (TSSs) are highly coordinated with distinctively transcriptional activities. Bivalent promoters gradually increase, while repressive promoters gradually decrease. High CpG (HCG) promoters of active genes are characterized by nucleosome depletion at TSSs, while low CpG (LCG) promoters exhibit the opposite characteristics. In addition, we show that vitamin C (VC) promotes reorganizations of canonical, H3K4me3- and H3K27me3-modified nucleosomes on specific genes during transition from pre-iPSCs to iPSCs. These data demonstrate that pre-iPSCs have a more open and phased chromatin architecture than that of MEFs and iPSCs. Finally, this study reveals the dynamics and critical roles of nucleosome positioning and chromatin organization in gene regulation during reprogramming.
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Kaimeng
authors.initials: K
authors.lastname: Huang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Mingze
authors.initials: M
authors.lastname: Yao
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Maryland, 21205, USA.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of RNA Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Guangzhou, 510530, China.
authors.forename: Biliang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Jiekai
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Pan
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: Key Laboratory of Regenerative Biology, CAS Center for Excellence in Molecular Cell Science, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yao
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D051379:Mice; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D008239:Lysine; D001205:Ascorbic Acid