Chromatin Accessibility Dynamics during iPSC Reprogramming

被引：161

作者：

Li, Dongwei ^{[1
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Liu, Jing ^{[1
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Yang, Xuejie ^{[1
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]}

Zhou, Chunhua ^{[1
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]}

Guo, Jing ^{[1
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Wu, Chuman ^{[1
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Qin, Yue ^{[1
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]}

Guo, Lin ^{[1
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He, Jiangping ^{[1
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Yu, Shenyong ^{[1
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Liu, He ^{[1
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Wang, Xiaoshan ^{[1
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Wu, Fang ^{[1
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Kuang, Junqi ^{[1
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Hutchins, Andrew P. ^{[1
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Chen, Jiekai ^{[1
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Pei, Duanqing ^{[1
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]}

机构：

[1] Chinese Acad Sci, CAS Key Lab Regenerat Biol, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, CAS Key Lab Regenerat Biol, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Hlth, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Acad Sci, Guangdong Prov Key Lab Stem Cell & Regenerat Med, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed, Guangzhou 510530, Guangdong, Peoples R China

[4] Chinese Acad Sci, Guangdong Prov Key Lab Stem Cell & Regenerat Med, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Hlth, Guangzhou 510530, Guangdong, Peoples R China

[5] Guangzhou Med Univ, Chinese Acad Sci, Joint Sch Life Sci, Guangzhou Inst Biomed, Guangzhou 511436, Guangdong, Peoples R China

[6] Guangzhou Med Univ, Chinese Acad Sci, Joint Sch Life Sci, Guangzhou Inst Hlth, Guangzhou 511436, Guangdong, Peoples R China

[7] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[8] Chinese Acad Sci, GUANGZHOU Regenerat Med & Hlth Lab, Guangzhou Inst Biomed, Guangzhou 510530, Guangdong, Peoples R China

[9] Chinese Acad Sci, GUANGZHOU Regenerat Med & Hlth Lab, Guangzhou Inst Hlth, Guangzhou 510530, Guangdong, Peoples R China

来源：

CELL STEM CELL | 2017年 / 21卷 / 06期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

PLURIPOTENT STEM-CELLS; GLOBAL GENE-EXPRESSION; DEEP-SEQUENCING DATA; RNA-SEQ DATA; SOMATIC-CELLS; GENOME; INDUCTION; BINDING; MOUSE; OCT4;

D O I：

10.1016/j.stem.2017.10.012

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSKdriven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift andfacilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.

引用

页码：819 / +

页数：21

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