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 crucial role in terminal differentiation of committed myoblasts into mature myocytes. 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 gene in differentiated cells correlates with MEF2 and NF1 binding to their cognate 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 demonstrated by expression of antisense MEF2 RNA which repressed MEF2 and Myf5-mediated MEF2 site-dependent reporter gene activation and the synergistic transactivation of a myogenin CAT reporter by Myf5 and MEF2. Adenovirus E1A which has previously been shown to specifically interfere with myogenin gene transcription also inhibited the cooperative transactivation by Myf5/MEF2 and MEF2. Consistently, coimmunoprecipitation studies revealed impaired MEF2/Myf5 protein-protein interactions. These results support a model of transcriptional activation and stabilization of myogenin expression in which DNA-bound MEF2 recruits myogenic bHLH factors into an active but E1A-sensitive transcription factor complex.
Johanson
M
M
University of Uppsala, BMC, Husargatan 3, Uppsala, 75124, Sweden.
Meents
H
H
Ragge
K
K
Buchberger
A
A
Arnold
H H
HH
Sandmöller
A
A
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000235:genetics*; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016385:TATA Box; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase