CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells  

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作  者:Shixin Gong Gongcheng Hu Rong Guo Jie Zhang Yiqi Yang Binrui Ji Gang Li Hongjie Yao 

机构地区:[1]Center for Health Research,Joint School of Life Sciences,CAS Key Laboratory of Regenerative Biology,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou Medical University,Guangzhou,China [2]Department of Life Sciences,Changzhi University,Changzhi,China [3]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,China [4]Institute of Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing,China [5]University of Chinese Academy of Sciences,Beijing,China [6]Cancer Centre,Faculty of Health Sciences,MoE Frontier Science Centre for Precision Oncology,University of Macao,Taipa,Macao SAR,China

出  处:《Cell Regeneration》2022年第1期348-364,共17页细胞再生(英文)

基  金:This work was supported in part by grants from the National Key R&D Program of China(2021YFA1100300);Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010502);National Natural Science Foundation of China(31925009,U21A20195,32000424,32100462,32100463,and 81902885);Science and Technology Planning Project of Guangdong Province,China(2019B020234004,2019A050510004 and 2020B1212060052);Macao Science and Technology Development Fund(FDCT0107/2019/A2).

摘  要:The CCCTC-binding factor(CTCF)protein and its modified forms regulate gene expression and genome organization.However,information on CTCF acetylation and its biological function is still lacking.Here,we show that CTCF can be acetylated at lysine 20(CTCF-K20)by CREB-binding protein(CBP)and deacetylated by histone deacetylase 6(HDAC6).CTCF-K20 is required for the CTCF interaction with CBP.A CTCF point mutation at lysine 20 had no effect on self-renewal but blocked the mesoderm differentiation of mouse embryonic stem cells(mESCs).The CTCF-K20 mutation reduced CTCF binding to the promoters and enhancers of genes associated with early cardiac mesoderm differentia-tion,resulting in diminished chromatin accessibility and decreased enhancer-promoter interactions,impairing gene expression.In summary,this study reveals the important roles of CTCF-K20 in regulating CTCF genomic functions and mESC differentiation into mesoderm.

关 键 词:CTCF CTCF acetylation CBP HDAC6 Early cardiac mesoderm differentiation 

分 类 号:R329.2[医药卫生—人体解剖和组织胚胎学]

 

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