Premium
An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis
Author(s) -
Innocenzi Anna,
Latella Lucia,
Messina Graziella,
Simonatto Marta,
Marullo Fabrizia,
Berghella Libera,
Poizat Coralie,
Shu ChihWen,
Wang Jean Y J,
Puri Pier Lorenzo,
Cossu Giulio
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.195
Subject(s) - myod , myf5 , myogenesis , pitx2 , myogenin , biology , myod protein , microbiology and biotechnology , phosphorylation , myogenic regulatory factors , myocyte , transcription factor , genetics , gene , homeobox
Despite having distinct expression patterns and phenotypes in mutant mice, the myogenic regulatory factors Myf5 and MyoD have been considered to be functionally equivalent. Here, we report that these factors have a different response to DNA damage, due to the presence in MyoD and absence in Myf5 of a consensus site for Abl ‐mediated tyrosine phosphorylation that inhibits MyoD activity in response to DNA damage. Genotoxins failed to repress skeletal myogenesis in MyoD ‐null embryos; reintroduction of wild‐type MyoD , but not mutant Abl phosphorylation‐resistant MyoD , restored the DNA‐damage‐dependent inhibition of muscle differentiation. Conversely, introduction of the Abl‐responsive phosphorylation motif converts Myf5 into a DNA‐damage‐sensitive transcription factor. Gene‐dosage‐dependent reduction of Abl kinase activity in MyoD‐expressing cells attenuated the DNA‐damage‐dependent inhibition of myogenesis. The presence of a DNA‐damage‐responsive phosphorylation motif in vertebrate, but not in invertebrate MyoD suggests an evolved response to environmental stress, originated from basic helix–loop–helix gene duplication in vertebrate myogenesis.