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

Kaimeng Huang; Xiaobai Zhang; Jiejun Shi; Mingze Yao; Jiannan Lin; Jiao Li; He Liu; Huanhuan Li; Guang Shi; Zhibin Wang; Biliang Zhang; Jiekai Chen; Guangjin Pan; Cizhong Jiang; Duanqing Pei; Hongjie Yao

doi:10.1038/srep17691

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

Kaimeng Huang, Xiaobai Zhang, Jiejun Shi, Mingze Yao, Jiannan Lin, Jiao Li, He Liu, Huanhuan Li, Guang Shi, Zhibin Wang, Biliang Zhang, Jiekai Chen, Guangjin Pan, Cizhong Jiang, Duanqing Pei, Hongjie Yao

Bloomberg School of Public Health

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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.

Original language	English (US)
Article number	17691
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep17691
State	Published - Dec 7 2015

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Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells. / Huang, Kaimeng; Zhang, Xiaobai; Shi, Jiejun; Yao, Mingze; Lin, Jiannan; Li, Jiao; Liu, He; Li, Huanhuan; Shi, Guang; Wang, Zhibin; Zhang, Biliang; Chen, Jiekai; Pan, Guangjin; Jiang, Cizhong; Pei, Duanqing; Yao, Hongjie.

In: Scientific reports, Vol. 5, 17691, 07.12.2015.

Research output: Contribution to journal › Article › peer-review

Huang, Kaimeng ; Zhang, Xiaobai ; Shi, Jiejun ; Yao, Mingze ; Lin, Jiannan ; Li, Jiao ; Liu, He ; Li, Huanhuan ; Shi, Guang ; Wang, Zhibin ; Zhang, Biliang ; Chen, Jiekai ; Pan, Guangjin ; Jiang, Cizhong ; Pei, Duanqing ; Yao, Hongjie. / Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells. In: Scientific reports. 2015 ; Vol. 5.

@article{25be04be49a047939078fc0b0951a324,

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.",

author = "Kaimeng Huang and Xiaobai Zhang and Jiejun Shi and Mingze Yao and Jiannan Lin and Jiao Li and He Liu and Huanhuan Li and Guang Shi and Zhibin Wang and Biliang Zhang and Jiekai Chen and Guangjin Pan and Cizhong Jiang and Duanqing Pei and Hongjie Yao",

note = "Funding Information: We thank Dr. Guohong Li for his comments and Dr. Andrew P. Hutchins for critical reading on this paper. This work was supported in part by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020401), the Ministry of Science and Technology of China (2015CB964800, 2014CB965200 and 2012AA020405), National Natural Science Foundation of China (31271391, 31471210, 81201580, 91213304, 31301082, 91019017, 31530038 and 31200952), Ministry of Science and Technology International Technology Cooperation Program (2012DFH30050), Introduced Innovative R&D Team Program of Guangdong Province (201001Y0104789252), Natural Science Foundation of Guangdong Province (2015A030308003), the Key Research Program of the Chinese Academy of Sciences (KJZD-EW-L01-3), Science and Technology Program of Guangzhou City (7415627430902) and the One Hundred Talents Project of the Chinese Academy of Sciences (to H.Y). Z.W. was supported by JHSPH Department of Environmental Health Science. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.",

year = "2015",

month = dec,

day = "7",

doi = "10.1038/srep17691",

language = "English (US)",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells

AU - Huang, Kaimeng

AU - Zhang, Xiaobai

AU - Shi, Jiejun

AU - Yao, Mingze

AU - Lin, Jiannan

AU - Li, Jiao

AU - Liu, He

AU - Li, Huanhuan

AU - Shi, Guang

AU - Wang, Zhibin

AU - Zhang, Biliang

AU - Chen, Jiekai

AU - Pan, Guangjin

AU - Jiang, Cizhong

AU - Pei, Duanqing

AU - Yao, Hongjie

N1 - Funding Information: We thank Dr. Guohong Li for his comments and Dr. Andrew P. Hutchins for critical reading on this paper. This work was supported in part by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020401), the Ministry of Science and Technology of China (2015CB964800, 2014CB965200 and 2012AA020405), National Natural Science Foundation of China (31271391, 31471210, 81201580, 91213304, 31301082, 91019017, 31530038 and 31200952), Ministry of Science and Technology International Technology Cooperation Program (2012DFH30050), Introduced Innovative R&D Team Program of Guangdong Province (201001Y0104789252), Natural Science Foundation of Guangdong Province (2015A030308003), the Key Research Program of the Chinese Academy of Sciences (KJZD-EW-L01-3), Science and Technology Program of Guangzhou City (7415627430902) and the One Hundred Talents Project of the Chinese Academy of Sciences (to H.Y). Z.W. was supported by JHSPH Department of Environmental Health Science. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

PY - 2015/12/7

Y1 - 2015/12/7

N2 - 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.

AB - 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.

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

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