Regulation of heterochromatin remodelling and myogenin expression during muscle differentiation by FAK interaction with MBD2

Shi Wen Luo, Chun Zhang, Bin Zhang, Chang Hoon Kim, Yuan Zheng Qiu, Quansheng Du, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Focal adhesion kinase (FAK), a major cell adhesion-activated tyrosine kinase, has an important function in cell adhesion and migration. Here, we report a new signalling of FAK in regulating chromatin remodelling by its interaction with MBD2 (methyl CpG-binding protein 2), underlying FAK regulation of myogenin expression and muscle differentiation. FAK interacts with MBD2 in vitro, in myotubes, and in isolated muscle fibres. Such an interaction, increased in myotubes exposed to oxidative stress, enhances FAK nuclear localization. The nuclear FAK-MBD2 complexes alter heterochromatin reorganization and decrease MBD2 association with HDAC1 (histone deacetylase complex 1) and methyl CpG site in the myogenin promoter, thus, inducing myogenin expression. In line with this view are observations that blocking FAK nuclear localization by expressing dominant negative MBD2 or suppression of FAK expression by its miRNA in C2C12 cells attenuates myogenin induction and/or impairs muscle-terminal differentiation. Together, these results suggest an earlier unrecognized role of FAK in regulating chromatin remodelling that is important for myogenin expression and muscle-terminal differentiation, reveal a new mechanism of MBD2 regulation by FAK family tyrosine kinases, and provide a link between cell adhesion and chromatin remodelling.

Original languageEnglish (US)
Pages (from-to)2568-2582
Number of pages15
JournalEMBO Journal
Volume28
Issue number17
DOIs
StatePublished - Sep 2 2009

Fingerprint

Myogenin
Focal Adhesion Protein-Tyrosine Kinases
Heterochromatin
Muscle
Muscles
Chromatin Assembly and Disassembly
Cell adhesion
Cell Adhesion
Chromatin
Skeletal Muscle Fibers
Protein-Tyrosine Kinases
Methyl-CpG-Binding Protein 2
Histone Deacetylase 1
Histone Deacetylases
Oxidative stress
MicroRNAs
Cell Movement
Oxidative Stress
Association reactions

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Regulation of heterochromatin remodelling and myogenin expression during muscle differentiation by FAK interaction with MBD2. / Luo, Shi Wen; Zhang, Chun; Zhang, Bin; Kim, Chang Hoon; Qiu, Yuan Zheng; Du, Quansheng; Mei, Lin; Xiong, Wencheng.

In: EMBO Journal, Vol. 28, No. 17, 02.09.2009, p. 2568-2582.

Research output: Contribution to journalArticle

Luo, Shi Wen ; Zhang, Chun ; Zhang, Bin ; Kim, Chang Hoon ; Qiu, Yuan Zheng ; Du, Quansheng ; Mei, Lin ; Xiong, Wencheng. / Regulation of heterochromatin remodelling and myogenin expression during muscle differentiation by FAK interaction with MBD2. In: EMBO Journal. 2009 ; Vol. 28, No. 17. pp. 2568-2582.
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