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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number17691
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 7 2015

Fingerprint

Induced Pluripotent Stem Cells
Nucleosomes
Chromatin
Fibroblasts
Transcription Initiation Site
Histones
Methylation
Genes
Histone Code
Cellular Reprogramming
Intergenic DNA
Genetic Promoter Regions
Ascorbic Acid
Genome

ASJC Scopus subject areas

  • General

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 journalArticle

Huang, K, Zhang, X, Shi, J, Yao, M, Lin, J, Li, J, Liu, H, Li, H, Shi, G, Wang, Z, Zhang, B, Chen, J, Pan, G, Jiang, C, Pei, D & Yao, H 2015, 'Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells', Scientific Reports, vol. 5, 17691. https://doi.org/10.1038/srep17691
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",
year = "2015",
month = "12",
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

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 -