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

Gong S.; Hu G.; Guo R.Zhang J.Yang Y.Ji B.Li G.Yao H.

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

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© 2022, The Author(s).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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《cell regeneration》 |2022年第1期|共页
作者
Gong S.; Hu G.; Guo R.Zhang J.Yang Y.Ji B.Li G.Yao H.;
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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;

Department of Life Sciences Changzhi University;

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 SciencesInstitute of Stem Cell and Regeneration Chinese Academy of SciencesUniversity of Chinese Academy of SciencesCancer Centre Faculty of Health Sciences MoE Frontier Science Centre for Precision Oncology University of Macau;

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CBP; CTCF; CTCF acetylation; Early cardiac mesoderm differentiation; HDAC6;

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1. The SHB adapter protein is required for normal maturation of mesoderm during in vitro differentiation of embryonic stem cells. [J] . Kriz V, Agren N, Lindholm CKLenell SSaldeen JMares JWelsh M The Journal of biological chemistry . 2006,第45期

机译：The SHB adapter protein is required for normal maturation of mesoderm during in vitro differentiation of embryonic stem cells.
2. Efficient derivation of lateral plate and paraxial mesoderm subtypes from human embryonic stem cells through GSKi-mediated differentiation [J] . TanJ.Y., SriramG., RufaihahA.J.NeohK.G.CaoT. Stem cells and development . 2013,第13期

机译：Efficient derivation of lateral plate and paraxial mesoderm subtypes from human embryonic stem cells through GSKi-mediated differentiation
3. Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. [J] . Jagtap S, Meganathan K, Gaspar JWagh VWinkler JHescheler JSachinidis A British Journal of Pharmacology . 2011,第8期

机译：Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation.
4. Mechanisms underlying the self-renewal characteristic and cardiac differentiation of mouse embryonic stem cells. [O] . 2009

机译：mechanisms underlying the self-renewal characteristic and cardiac differentiation of mouse embryonic stem cells.

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

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