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  • The differentiation of muscle cells is regulated by many factors, including the MyoD/MEF2 family of transcription factors. The MyoD/MEF2 dimer binds to promoters to activate genes involved in muscle cell differentiation. One of the factors that regulates the role of MyoD/MEF2 in myogenesis is the protein MEF2-interacting transcription repressor (MITR), a transcriptional repressor. When MITR is bound to MEF2, myogenesis genes are repressed rather than being activated. The transcriptional repression by MITR occurs in part at least through interaction with the CtBP (carboxy-terminal binding protein) corepressor. The inhibitory activity of MITR is itself regulated by the calmodulin dependent protein kinase CAMK. When CAMK is activated by factors such as IGF-1, it phosphorylates two specific residues in MITR, ser218 and ser448. Phosphorylated MITR does not bind to MEF2, but does bind to the protein 14-3-3, helping to block the repression of myogenesis. CAMK also plays a role in myogenesis through phosphorylation of histone deacetylase (HDAC), in which HDAC alters chromatin to repress myogenesis. Like MITR, phosphorylation of HDAC removes the repression, allowing myogenesis to continue. MITR shares sequence homology with HDAC, but itself lacks the enzyme motif. (This definition may be outdated - see the DesignNote.)
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