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 | |
| State | Published - Dec 7 2015 |
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Cite this
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
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84949503081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949503081&partnerID=8YFLogxK
U2 - 10.1038/srep17691
DO - 10.1038/srep17691
M3 - Article
C2 - 26639176
AN - SCOPUS:84949503081
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 17691
ER -