The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes
文献类型：期刊论文
| 作者 | Zhao, Haixin1,2; Liu, Xinyuan2; Jin, Ying2,4; Han, Zhijun3; Wei, Gang3; Gu, Junjie4; Tang, Fan4; , |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2017 |
| 卷号 | 292期号:20页码:8507-8519 |
| 关键词 | breast cancer subtype methylation pattern multi-class classification |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M116.770248 |
| 文献子类 | Article |
| 英文摘要 | The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in ESC regulation remains elusive. Here we report that Chd4 is required for the maintenance of ESC self-renewal. RNAi-mediated silencing of Chd4 disrupted self-renewal and up-regulated lineage commitment-associated genes under self-renewal culture conditions. During ESC differentiation in embryoid body formation, we observed significantly stronger induction of differentiation-associated genes in Chd4-deficient cells. The phenotype was different from that caused by the deletion of Mbd3, another subunit of the NuRD complex. Transcriptomic analyses revealed that Chd4 secured ESC identity by controlling the expression of subsets of pluripotency- and differentiation-associated genes. Importantly, Chd4 repressed the transcription of T box protein 3 (Tbx3), a transcription factor with important functions in ESC fate determination. Tbx3 knockdown partially rescued aberrant activation of differentiation-associated genes, especially of endoderm-associated genes, induced by Chd4 depletion. Moreover, we identified an interaction of Chd4 with the histone variant H2A. Z. This variant stabilized Chd4 by inhibiting Chd4 protein degradation through the ubiquitin-proteasome pathway. Collectively, this study identifies the Chd4-Tbx3 axis in controlling ESC fate and a role of H2A. Z in maintaining the stability of Chd4 proteins. |
| 学科主题 | Biochemistry & Molecular Biology |
| WOS关键词 | SELF-RENEWAL ; TRANSCRIPTIONAL ACTIVITY ; DEACETYLASE COMPLEX ; ES CELLS ; NURD ; COMPONENT ; NANOG ; MBD3 ; ACTIVATION ; REPRESSION |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31480430 |
| WOS记录号 | WOS:000401788600033 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1282]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Chinese Acad Sci,Inst Hlth Sci,Shanghai Inst Biol, Key Lab Stem Cell Biol,CAS Ctr Excellence Mol Cel, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Lab Mol Dev Biol, Shanghai 200025, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhao, Haixin,Liu, Xinyuan,Jin, Ying,et al. The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(20):8507-8519. |
| APA | Zhao, Haixin.,Liu, Xinyuan.,Jin, Ying.,Han, Zhijun.,Wei, Gang.,...&,.(2017).The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes.JOURNAL OF BIOLOGICAL CHEMISTRY,292(20),8507-8519. |
| MLA | Zhao, Haixin,et al."The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes".JOURNAL OF BIOLOGICAL CHEMISTRY 292.20(2017):8507-8519. |
入库方式： OAI收割
来源：上海营养与健康研究所
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