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Sci Rep. 2015 Dec 7;5:17691. doi: 10.1038/srep17691.

Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells.

Huang K1,2, Zhang X3, Shi J3, Yao M1,2, Lin J3, Li J1,2, Liu H1,2, Li H1,2, Shi G1,2, Wang Z4, Zhang B5, Chen J1,2, Pan G1,2, Jiang C3, Pei D1,2, Yao H1,2.

Author information

1
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.
2
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.
3
School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
4
Department of Environmental Health Sciences, Johns Hopkins University, Maryland, 21205, USA.
5
Laboratory of RNA Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Guangzhou, 510530, China.

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.

PMID:
26639176
PMCID:
PMC4671053
DOI:
10.1038/srep17691
[Indexed for MEDLINE]
Free PMC Article

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