Abstract:
:Skeletal muscle development requires the coordinated expression of numerous transcription factors to control the specification of the muscle fate in mesodermal cells and the differentiation of the committed myoblasts into functional contractile fibers. The bHLH transcription factor MyoD plays a key role in these processes, since its forced expression is sufficient to induce the myogenesis in a variety of non-muscle cells in culture. Consistent with this observation, the majority of skeletal muscle genes require MyoD to activate their own transcription. In order to identify novel MyoD-target genes we generated C2C12 MyoD-silenced clones, and used a muscle-specific cDNA microarray to study the induced modifications of the transcriptional profile. Gene expression was analyzed at three different stages in differentiating MyoD(-)C2C12 myoblasts. These microarray data sets identified many additional uncharacterized downstream MyoD transcripts that may play important functions in muscle cell differentiation. Among these genes, we concentrated our study on the cell cycle regulators Cdkn1c and calcyclin and on the muscle-specific putative myogenic regulator Ankrd2. Bioinformatic and functional studies on the promoters of these genes clarified their dependence on MyoD activity. Clues of other regulatory mechanisms that might interact with the principal bHLH transcription factor have been revealed by the unexpected up-regulation in MyoD(-) cells of these novel (and other) target transcripts, at the differentiation stage in which MyoD became normally down-regulated.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Bean C,Salamon M,Raffaello A,Campanaro S,Pallavicini A,Lanfranchi Gdoi
10.1016/j.jmb.2005.03.063keywords:
subject
Has Abstractpub_date
2005-06-03 00:00:00pages
349-66issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(05)00353-0journal_volume
349pub_type
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