Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products

Peter Cserjesi, Eric N. Olson

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

The myocyte-specific enhancer-binding factor MEF-2 is a nuclear factor that interacts with a conserved element in the muscle creatine kinase and myosin light-chain 1/3 enhancers (L. A. Gossett, D. J. Kelvin, E. A. Sternberg, and E. N. Olson, Mol. Cell. Biol. 9:5022-5033, 1989). We show in this study that MEF-2 is regulated by the myogenic regulatory factor myogenin and that mitogenic signals block this regulatory interaction. Induction of MEF-2 by myogenin occurs in transfected 10T1/2 cells that have been converted to myoblasts by myogenin, as well as in CV-1 kidney cells that do not activate the myogenic program in response to myogenin. Through mutagenesis of the MEF-2 site, we further defined the binding site requirements for MEF-2 and identified potential MEF-2 sites within numerous muscle-specific regulatory regions. The MEF-2 site was also found to bind a ubiquitous nuclear factor whose binding specificity was similar to but distinct from that of MEF-2. Our results reveal that MEF-2 is controlled, either directly or indirectly, by a myogenin-dependent regulatory pathway and suggest that growth factor signals suppress MEF-2 expression through repression of myogenin expression or activity. The ability of myogenin to induce MEF-2 activity in CV-1 cells, which do not activate downstream genes associated with terminal differentiation, also demonstrates that myogenin retains limited function within cell types that are nonpermissive for myogenesis and suggests that MEF-2 is regulated independently of other muscle-specific genes.

Original languageEnglish (US)
Pages (from-to)4854-4862
Number of pages9
JournalMolecular and Cellular Biology
Volume11
Issue number10
StatePublished - 1991

Fingerprint

MEF2 Transcription Factors
Myogenin
Muscles
Genes
Myogenic Regulatory Factors
MM Form Creatine Kinase
Myosin Light Chains
Muscle Development
Myoblasts
Nucleic Acid Regulatory Sequences
Mutagenesis
Intercellular Signaling Peptides and Proteins
Binding Sites
Kidney

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. / Cserjesi, Peter; Olson, Eric N.

In: Molecular and Cellular Biology, Vol. 11, No. 10, 1991, p. 4854-4862.

Research output: Contribution to journalArticle

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