A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle

Libera Berghella, Luciana De Angelis, Tristan De Buysscher, Ali Mortazavi, Stefano Biressi, Sonia V. Forcales, Dario Sirabella, Giulio Cossu, Barbara J. Wold

Research output: Contribution to journalArticle

Abstract

Myogenin is the dominant transcriptional regulator of embryonic and fetal muscle differentiation and during maturation is profoundly down-regulated. We show that a highly conserved 17-bp DNA cis-acting sequence element located upstream of the myogenin promoter (myogHCE) is essential for postnatal repression of myogenin in transgenic animals. We present multiple lines of evidence supporting the idea that repression is mediated by the Y-box protein MSY-3. Electroporation in vivo shows that myogHCE and MSY-3 are required for postnatal repression. We further show that, in the C2C12 cell culture system, ectopic MSY-3 can repress differentiation, while reduced MSY-3 promotes premature differentiation. MSY-3 binds myogHCE simultaneously with the homeodomain protein Pbx in postnatal innervated muscle. We therefore propose a model in which the myogHCE motif operates as a switch by specifying opposing functions; one that was shown previously is regulated by MyoD and Pbx and it specifies a chromatin opening, gene-activating function at the time myoblasts begin to differentiate; the other includes MYS-3 and Pbx, and it specifies a repression function that operates during and after postnatal muscle maturation in vivo and in myoblasts before they begin to differentiate.

Original languageEnglish
Pages (from-to)2125-2138
Number of pages14
JournalGenes and Development
Volume22
Issue number15
DOIs
Publication statusPublished - Aug 1 2008

Keywords

  • CsdA
  • Innervation
  • MSY-3
  • Muscle maturation
  • Myogenin
  • Y-box

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Berghella, L., De Angelis, L., De Buysscher, T., Mortazavi, A., Biressi, S., Forcales, S. V., Sirabella, D., Cossu, G., & Wold, B. J. (2008). A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle. Genes and Development, 22(15), 2125-2138. https://doi.org/10.1101/gad.468508