Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency

被引：51

作者：

Zhu, Fugui ^{[1
]}

Zhu, Qianshu ^{[2
]}

Ye, Dan ^{[1
]}

Zhang, Qingquan ^{[3
]}

Yang, Yiwei ^{[1
]}

Guo, Xudong ^{[1
,4
]}

Liu, Zhenping ^{[2
]}

Jiapaer, Zeyidan ^{[1
]}

Wan, Xiaoping ^{[5
]}

Wang, Guiying ^{[1
]}

Chen, Wen ^{[1
]}

Zhu, Songcheng ^{[1
]}

Jiang, Cizhong ^{[2
]}

Shi, Weiyang ^{[2
]}

Kang, Jiuhong ^{[1
,2
]}

机构：

[1] Tongji Univ, Sch Life Sci & Technol, Collaborat Innovat Ctr Brain Sci,Clin & Translat, Shanghai Matern & Infant Hlth Hosp 1,Shanghai Key, 1239 Siping Rd, Shanghai 200092, Peoples R China

[2] Tongji Univ, Sch Life Sci & Technol, 1239 Siping Rd, Shanghai 200092, Peoples R China

[3] Tongji Univ, Sch Med, East Hosp, Key Lab Arrhythmia,Minist Educ, Shanghai 200120, Peoples R China

[4] Tongji Univ, Sch Med, East Hosp, Inst Regenerat Med, Shanghai 200120, Peoples R China

[5] Shanghai First Matern & Infant Hlth Hosp, Shanghai 200120, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2018年 / 46卷 / 12期

基金：

中国国家自然科学基金;

关键词：

SELF-RENEWAL; REPRESSOR SIN3; MOUSE EMBRYOS; PAH2; DOMAIN; DNA; COREPRESSOR; TET1; DIFFERENTIATION; REGULATOR; COMPLEX;

D O I：

10.1093/nar/gky347

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sin3a is a core component of histone-deacetylation-activity-associated transcriptional repressor complex, playing important roles in early embryo development. Here, we reported that down-regulation of Sin3a led to the loss of embryonic stem cell (ESC) self-renewal and skewed differentiation into mesendoderm lineage. We found that Sin3a functioned as a transcriptional coactivator of the critical Nodal antagonist Lefty1 through interacting with Tet1 to de-methylate the Lefty1 promoter. Further studies showed that two amino acid residues (Phe147, Phe182) in the PAH1 domain of Sin3a are essential for Sin3a-Tet1 interaction and its activity in regulating pluripotency. Furthermore, genome-wide analyses of Sin3a, Tet1 and Pol II ChIP-seq and of 5mC MeDIP-seq revealed that Sin3a acted with Tet1 to facilitate the transcription of a set of their co-target genes. These results link Sin3a to epigenetic DNA modifications in transcriptional activation and have implications for understanding mechanisms underlying versatile functions of Sin3a in mouse ESCs.

引用

页码：6026 / 6040

页数：15

共 58 条

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