PCGF5 is required for neural differentiation of embryonic stem cells

被引：51

作者：

Yao, Mingze ^{[1
,2
]}

Zhou, Xueke ^{[1
,2
]}

Zhou, Jiajian ^{[3
]}

Gong, Shixin ^{[1
,2
]}

Hu, Gongcheng ^{[1
,2
]}

Li, Jiao ^{[1
,2
]}

Huang, Kaimeng ^{[1
,2
]}

Lai, Ping ^{[1
,2
]}

Shi, Guang ^{[1
,2
]}

Hutchins, Andrew P. ^{[4
]}

Sun, Hao ^{[3
]}

Wang, Huating ^{[5
]}

Yao, Hongjie ^{[1
,2
]}

机构：

[1] Guangzhou Med Univ, Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol,Joint Sch Life Sci, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Ctr Excellence Mol Cell Sci, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Dept Chem Pathol, Hong Kong 999077, Hong Kong, Peoples R China

[4] Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China

[5] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Dept Orthopaed & Traumatol, Hong Kong 999077, Hong Kong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

UBIQUITIN LIGASE ACTIVITY; SELF-RENEWAL; POLYCOMB; PRC1; EXPRESSION; REPRESSION; PROTEINS; RECRUITMENT; PRECURSORS; FATE;

D O I：

10.1038/s41467-018-03781-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-beta signaling pathway. PCGF5 loss-of-function impairs the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results suggest that PCGF5 might function as both a repressor for SMAD2/TGF-beta signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.

引用

页数：12

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