Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity

Jungseog Kang, Christian B. Gocke, Hongtao Yu

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background: Sumoylation has emerged as an important posttranslational regulatory mechanism for transcription factors and cofactors. Sumoylation of many transcription factors represses their transcriptional activities. The myocyte enhancer factor 2 (MEF2) family of transcription factors plays an important role in regulating gene expression during myogenesis and has been recently shown to be sumoylated. Results: Consistent with earlier reports, we show that sumoylation of MEF2C at K391 inhibits its transcriptional activity. Sumoylation of MEF2C does not block its DNA-binding activity. A small C-terminal fragment of MEF2C containing K391, referred to as delta-N2-MEF2C, is efficiently sumoylated and, when targeted to DNA, represses transcription at neighbouring promoters. Because delta-N2-MEF2C lacks the binding site for class II histone deacetylases (HDACs), this result suggests that sumoylation of MEF2C may help to recruit transcriptional repressors other than these HDACs. Intriguingly, we show that phosphorylation of S396 in MEF2C, a residue in close proximity to the major sumoylation site (K391) and known to be phosphorylated in vivo, enhances sumoylation of delta- N2-MEF2C in vitro. The S396A mutation reduces sumoylation of MEF2C in vivo and enhances the transcription activity of MEF2C in reporter assays. Conclusion: We propose that phosphorylation of MEF2C at S396 facilitates its sumoylation at K391, which in turn recruits yet unidentified co-repressors to inhibit transcription. Our studies further suggest that sumoylation motifs containing a phosphorylated serine or an acidic residue at the +5 position might be more efficiently sumoylated.

Original languageEnglish (US)
Article number5
JournalBMC Biochemistry
Volume7
DOIs
StatePublished - Feb 14 2006

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Sumoylation
Phosphorylation
Transcription
Histone Deacetylases
Transcription Factors
MEF2 Transcription Factors
Co-Repressor Proteins
DNA
Gene expression
Serine
Assays
Binding Sites
Muscle Development

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Molecular Biology

Cite this

Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity. / Kang, Jungseog; Gocke, Christian B.; Yu, Hongtao.

In: BMC Biochemistry, Vol. 7, 5, 14.02.2006.

Research output: Contribution to journalArticle

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