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

Abstract 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 (...

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Main Authors: Shixin Gong, Gongcheng Hu, Rong Guo, Jie Zhang, Yiqi Yang, Binrui Ji, Gang Li, Hongjie Yao
Format: Article
Language:English
Published: SpringerOpen 2022-09-01
Series:Cell Regeneration
Subjects:
Online Access:https://doi.org/10.1186/s13619-022-00131-w
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author Shixin Gong
Gongcheng Hu
Rong Guo
Jie Zhang
Yiqi Yang
Binrui Ji
Gang Li
Hongjie Yao
author_facet Shixin Gong
Gongcheng Hu
Rong Guo
Jie Zhang
Yiqi Yang
Binrui Ji
Gang Li
Hongjie Yao
author_sort Shixin Gong
collection DOAJ
description Abstract 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 differentiation, 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.
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spelling doaj.art-2c8ab2d5a5604f80abfdf3b6e448f5ca2022-12-22T04:25:51ZengSpringerOpenCell Regeneration2045-97692022-09-0111111710.1186/s13619-022-00131-wCTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cellsShixin Gong0Gongcheng Hu1Rong Guo2Jie Zhang3Yiqi Yang4Binrui Ji5Gang Li6Hongjie Yao7Center 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 UniversityCenter 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 UniversityCenter 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 UniversityCenter 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 UniversityCancer Centre, Faculty of Health Sciences, MoE Frontier Science Centre for Precision Oncology, University of MacauCenter 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 UniversityCancer Centre, Faculty of Health Sciences, MoE Frontier Science Centre for Precision Oncology, University of MacauCenter 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 UniversityAbstract 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 differentiation, 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.https://doi.org/10.1186/s13619-022-00131-wCTCFCTCF acetylationCBPHDAC6Early cardiac mesoderm differentiation
spellingShingle Shixin Gong
Gongcheng Hu
Rong Guo
Jie Zhang
Yiqi Yang
Binrui Ji
Gang Li
Hongjie Yao
CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
Cell Regeneration
CTCF
CTCF acetylation
CBP
HDAC6
Early cardiac mesoderm differentiation
title CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
title_full CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
title_fullStr CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
title_full_unstemmed CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
title_short CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
title_sort ctcf acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
topic CTCF
CTCF acetylation
CBP
HDAC6
Early cardiac mesoderm differentiation
url https://doi.org/10.1186/s13619-022-00131-w
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