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Mol. Cells 2012; 34(2): 133-142

Published online August 31, 2012

https://doi.org/10.1007/s10059-012-2286-1

© The Korean Society for Molecular and Cellular Biology

Effects of Myogenin on Expression of Late Muscle Genes through MyoD-Dependent Chromatin Remodeling Ability of Myogenin

Chao Du1, Ya-Qiong Jin1, Jun-Juan Qi1, Zhen-Xing Ji1, Shu-Yan Li1, Guo-Shun An1, Hong-Ti Jia1,2, and Ju-Hua Ni1,*

1Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, People’s Republic of China, 2Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, Beijing 100069, People’s Republic of China

Correspondence to : *Correspondence: juhuani@bjmu.edu.cn

Received: December 20, 2011; Revised: May 26, 2012; Accepted: June 7, 2012

Abstract

MyoD and myogenin (Myog) recognize sets of distinct but overlapping target genes and play different roles in skeletal muscle differentiation. MyoD is sufficient for near-full expression of early targets, while Myog can only partially enhance expression of MyoD-initiated late muscle genes. However, the way in which Myog enhances the expression of MyoD-initiated late muscle genes remains unclear. Here, we examine the effects of Myog on chromatin remodeling at late muscle gene promoters and their activation within chromatin environment. Chromatin immunoprecipitation (ChIP) assay showed that Myog selectively bound to the regulatory sequences of late muscle genes. Overexpres-sion of Myog was found to overcome sodium butyrate-inhibited chromatin at late muscle genes in differ-entiating C2C12 myoblasts, shifting the transcriptional activation of these genes to an earlier time period. Furthermore, overexpression of Myog led to increased hyperacetylation of core histone H4 in differentiating C2C12 myoblasts but not NIH3T3 fibroblasts, and hyperacetylated H4 was associated directly with the late muscle genes in differentiating C2C12, indicating that Myog can induce chromatin remodeling in the presence of MyoD. In addition, co-immunopre-cipitation (CoIP) revealed that Myog was associated with the nuclear protein Brd4 in differentiating C2C12 myoblasts. Together, these results suggest that Myog enhances the expression of MyoD-initiated late muscle genes through MyoD-dependent ability of Myog to induce chromatin remodeling, in which Myog-Brd4 interaction may be involved.

Keywords chromatin remodeling, gene regulation, myogenin, myogenesis, MyoD

Article

Research Article

Mol. Cells 2012; 34(2): 133-142

Published online August 31, 2012 https://doi.org/10.1007/s10059-012-2286-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Effects of Myogenin on Expression of Late Muscle Genes through MyoD-Dependent Chromatin Remodeling Ability of Myogenin

Chao Du1, Ya-Qiong Jin1, Jun-Juan Qi1, Zhen-Xing Ji1, Shu-Yan Li1, Guo-Shun An1, Hong-Ti Jia1,2, and Ju-Hua Ni1,*

1Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, People’s Republic of China, 2Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, Beijing 100069, People’s Republic of China

Correspondence to:*Correspondence: juhuani@bjmu.edu.cn

Received: December 20, 2011; Revised: May 26, 2012; Accepted: June 7, 2012

Abstract

MyoD and myogenin (Myog) recognize sets of distinct but overlapping target genes and play different roles in skeletal muscle differentiation. MyoD is sufficient for near-full expression of early targets, while Myog can only partially enhance expression of MyoD-initiated late muscle genes. However, the way in which Myog enhances the expression of MyoD-initiated late muscle genes remains unclear. Here, we examine the effects of Myog on chromatin remodeling at late muscle gene promoters and their activation within chromatin environment. Chromatin immunoprecipitation (ChIP) assay showed that Myog selectively bound to the regulatory sequences of late muscle genes. Overexpres-sion of Myog was found to overcome sodium butyrate-inhibited chromatin at late muscle genes in differ-entiating C2C12 myoblasts, shifting the transcriptional activation of these genes to an earlier time period. Furthermore, overexpression of Myog led to increased hyperacetylation of core histone H4 in differentiating C2C12 myoblasts but not NIH3T3 fibroblasts, and hyperacetylated H4 was associated directly with the late muscle genes in differentiating C2C12, indicating that Myog can induce chromatin remodeling in the presence of MyoD. In addition, co-immunopre-cipitation (CoIP) revealed that Myog was associated with the nuclear protein Brd4 in differentiating C2C12 myoblasts. Together, these results suggest that Myog enhances the expression of MyoD-initiated late muscle genes through MyoD-dependent ability of Myog to induce chromatin remodeling, in which Myog-Brd4 interaction may be involved.

Keywords: chromatin remodeling, gene regulation, myogenin, myogenesis, MyoD

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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