Thedifferentiationofmusclecellsisregulatedbymanyfactors,includingtheMyoD/MEF2familyoftranscriptionfactors.TheMyoD/MEF2dimerbindstopromoterstoactivategenesinvolvedinmusclecelldifferentiation.OneofthefactorsthatregulatestheroleofMyoD/MEF2inmyogenesisistheproteinMEF2-interactingtranscriptionrepressor(MITR),atranscriptionalrepressor.WhenMITRisboundtoMEF2,myogenesisgenesarerepressedratherthanbeingactivated.ThetranscriptionalrepressionbyMITRoccursinpartatleastthroughinteractionwiththeCtBP(carboxy-terminalbindingprotein)corepressor.TheinhibitoryactivityofMITRisitselfregulatedbythecalmoldulindependentproteinkinaseCAMK.WhenCAMKisactivatedbyfactorssuchasIGF-1,itphosphorylatestwospecificresiduesinMITR,ser218andser448.PhosphorylatedMITRdoesnotbindtoMEF2,butdoesbindtotheprotein14-3-3,helpingtoblocktherepressionofmyogenesis.CAMKalsoplaysaroleinmyogenesisthroughphosphorylationofhistonedeacetylase(HDAC,seeControlofSkeletalMyogenesispathway),inwhichHDACalterschromatintorepressmyogenesis.LikeMITR,phosphorylationofHDACremovestherepression,allowingmyogenesistocontinue.MITRsharessequencehomologywithHDACs,butitselflackstheenzymemotif

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REFERENCES:Zhang,C.L.,McKinsey,T.A.,andOlson,E.N.ThetranscriptionalcorepressorMITRisasignal-responsiveinhibitorofmyogenesis.Proc.Natl.Acad.Sci.U.S.A.2001,98(13),7354-9Zhang,C.L.,McKinsey,T.A.,Lu,J.R.,andOlson,E.N.AssociationofCOOH-terminal-bindingprotein(CtBP)andMEF2-interactingtranscriptionrepressor(MITR)contributestotranscriptionalrepressionoftheMEF2transcriptionfactor.J.Biol.Chem.2001,276(1),35-9

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