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Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications.

Publication ,  Journal Article
Zhao, X; Sternsdorf, T; Bolger, TA; Evans, RM; Yao, T-P
Published in: Mol Cell Biol
October 2005

The class II deacetylase histone deacetylase 4 (HDAC4) negatively regulates the transcription factor MEF2. HDAC4 is believed to repress MEF2 transcriptional activity by binding to MEF2 and catalyzing local histone deacetylation. Here we report that HDAC4 also controls MEF2 by a novel SUMO E3 ligase activity. We show that HDAC4 interacts with the SUMO E2 conjugating enzyme Ubc9 and is itself sumoylated. The overexpression of HDAC4 leads to prominent MEF2 sumoylation in vivo, whereas recombinant HDAC4 stimulates MEF2 sumoylation in a reconstituted system in vitro. Importantly, HDAC4 promotes sumoylation on a lysine residue that is also subject to acetylation by a MEF2 coactivator, the acetyltransferase CBP, suggesting a possible interplay between acetylation and sumoylation in regulating MEF2 activity. Indeed, MEF2 acetylation is correlated with MEF2 activation and dynamically induced upon muscle cell differentiation, while sumoylation inhibits MEF2 transcriptional activity. Unexpectedly, we found that HDAC4 does not function as a MEF2 deacetylase. Instead, the NAD+-dependent deacetylase SIRT1 can potently induce MEF2 deacetylation. Our studies reveal a novel regulation of MEF2 transcriptional activity by two distinct classes of deacetylases that affect MEF2 sumoylation and acetylation.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 2005

Volume

25

Issue

19

Start / End Page

8456 / 8464

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transfection
  • Transcription, Genetic
  • Small Ubiquitin-Related Modifier Proteins
  • Sirtuins
  • Sirtuin 1
  • Repressor Proteins
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Plasmids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhao, X., Sternsdorf, T., Bolger, T. A., Evans, R. M., & Yao, T.-P. (2005). Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol, 25(19), 8456–8464. https://doi.org/10.1128/MCB.25.19.8456-8464.2005
Zhao, Xuan, Thomas Sternsdorf, Timothy A. Bolger, Ronald M. Evans, and Tso-Pang Yao. “Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications.Mol Cell Biol 25, no. 19 (October 2005): 8456–64. https://doi.org/10.1128/MCB.25.19.8456-8464.2005.
Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao T-P. Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol. 2005 Oct;25(19):8456–64.
Zhao, Xuan, et al. “Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications.Mol Cell Biol, vol. 25, no. 19, Oct. 2005, pp. 8456–64. Pubmed, doi:10.1128/MCB.25.19.8456-8464.2005.
Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao T-P. Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol. 2005 Oct;25(19):8456–8464.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 2005

Volume

25

Issue

19

Start / End Page

8456 / 8464

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transfection
  • Transcription, Genetic
  • Small Ubiquitin-Related Modifier Proteins
  • Sirtuins
  • Sirtuin 1
  • Repressor Proteins
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Plasmids