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

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

doi:10.1186/s13619-022-00131-w

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

Cell Regen. 2022 Sep 19;11(1):34. doi: 10.1186/s13619-022-00131-w.

Authors

Shixin Gong^#^{1

2

3

4}, Gongcheng Hu^#^{1

2

3

4}, Rong Guo^{1

3

4

5}, Jie Zhang^{1

3

4

5}, Yiqi Yang⁶, Binrui Ji^{1

3

4

5}, Gang Li⁶, Hongjie Yao^{7

8

9

10}

Affiliations

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 Macau, Taipa, Macau SAR, China.
⁷ 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. yao_hongjie@gibh.ac.cn.
⁸ 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. yao_hongjie@gibh.ac.cn.
⁹ Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. yao_hongjie@gibh.ac.cn.
¹⁰ University of Chinese Academy of Sciences, Beijing, China. yao_hongjie@gibh.ac.cn.

^# Contributed equally.

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.

Keywords: CBP; CTCF; CTCF acetylation; Early cardiac mesoderm differentiation; HDAC6.

Abstract

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