AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation

doi:10.1038/celldisc.2015.17

	AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation
	Qiao, Yunbo 1; Wang, Xiongjun 2; Wang, Ran 1; Li, Yuanyuan 1; Yu, Fang 1; Yang, Xianfa1,3 ; Song, Lu 1; Xu, Guoliang 4; Chin, Y. Eugene 2; Jing, Naihe1
	2015
发表期刊	CELL DISCOVERY
ISSN	2056-5968
卷号	1
发表状态	已发表
DOI	10.1038/celldisc.2015.17
摘要	AF9 mutations have been implicated in human neurodevelopmental diseases and murine Af9 mediates histone methylation during cortical neuron generation. However, AF9 function and related mechanisms in human neurodevelopment remain unknown. Here we show that AF9 is necessary and sufficient for human embryonic stem cell (hESC) neural differentiation and neurodevelopmental gene activation. The 5-methylcytosine (5mC) dioxygenase TET2, which was identified in an AF9-associated protein complex, physically interacted with AF9. Both AF9 and TET2 co-localized in 5-hydroxymethylcytosine (5hmC)-positive hESC-derived neurons and were required for appropriate hESC neural differentiation. Upon binding to AAC-containing motifs, AF9 recruited TET2 to occupy the common neurodevelopmental gene loci to direct 5mC-to-5hmC conversion, which was followed by sequential activation of neural target genes and hESC neural commitment. These findings define an AF9-TET2 regulatory complex for modulating human neural development and reveal a novel mechanism by which the AF9 recognition specificity and TET2 hydroxylation activity cooperate to control neurodevelopmental gene activation.
关键词	AF9 TET2 human embryonic stem cell neural differentiation 5-hydroxymethylcytosine
收录类别	SCI
语种	英语
资助项目	Chinese Postdoctoral Science Foundation[2013M541560]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000414776800017
出版者	NATURE PUBLISHING GROUP
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10056
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_景乃禾组生命科学与技术学院_博士生
通讯作者	Chin, Y. Eugene
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Biol Sci,Chinese Acad Sci, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai, Peoples R China 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Qiao, Yunbo,Wang, Xiongjun,Wang, Ran,et al. AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation[J]. CELL DISCOVERY,2015,1.
APA	Qiao, Yunbo.,Wang, Xiongjun.,Wang, Ran.,Li, Yuanyuan.,Yu, Fang.,...&Jing, Naihe.(2015).AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation.CELL DISCOVERY,1.
MLA	Qiao, Yunbo,et al."AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation".CELL DISCOVERY 1(2015).