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

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 re...

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Bibliographic Details
Published in:Genes & development 2008-08, Vol.22 (15), p.2125-2138
Main Authors: Berghella, Libera, De Angelis, Luciana, De Buysscher, Tristan, Mortazavi, Ali, Biressi, Stefano, Forcales, Sonia V, Sirabella, Dario, Cossu, Giulio, Wold, Barbara J
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line
DNA-Binding Proteins - metabolism
Electroporation
Gene Expression Regulation - physiology
Genetic Vectors
Homeodomain Proteins - metabolism
Lentivirus - genetics
Mice
Muscle, Skeletal - growth & development
Myoblasts - physiology
MyoD Protein - genetics
MyoD Protein - physiology
Myogenin - genetics
Myogenin - physiology
Pre-B-Cell Leukemia Transcription Factor 1
Research Paper
RNA-Binding Proteins - metabolism
Transcription Factors - metabolism
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.468508