Transcriptional activation of the myogenin gene by MEF2-mediated recruitment of Myf5 is inhibited by adenovirus E1A protein

The basic helix-loop-helix (bHLH) transcription factor myogenin plays a cru cial role in terminal differentiation of committed myoblasts into mature my ocytes, Transcriptional activation of the myogenin gene requires coordinate action of myocyte enhancer factor 2 (MEF2) proteins and the myogenic bHLH regulators, MyoD or Myf5. Here we show that transcription of the myogenin g ene in differentiated cells correlates with MEF2 and NF1 binding to their c ognate sites in the proximal myogenin promoter but not with binding of Myf5 or MyoD to the E-box. The importance of MEF2 activity was further demonstr ated by expression of antisense MEF2 RNA which repressed MEF2 and Myf5-medi ated MEF2 site-dependent reporter gene activation and the synergistic trans activation of a myogenin CAT reporter by Myf5 and MEF2. Adenovirus E1A whic h has previously been shown to specifically interfere with myogenin gene tr anscription also inhibited the cooperative transactivation by Myf5/MEF2 and MEF2. Consistently, coimmunoprecipitation studies revealed impaired MEF2/M yf5 protein-protein interactions. These results support a model of transcri ptional activation and stabilization of myogenin expression in which DNA-bo und MEF2 recruits myogenic bHLH factors into an active but EIA-sensitive tr anscription factor complex. (C) 1999 Academic Press.