REGULATORY ROLE OF MEF2D IN SERUM INDUCTION OF THE C-JUN PROMOTER

Serum induction of c-jun expression in HeLa cells requires a MEF2 site at -59 in the c-jun promoter. MEF2 sites, found in many muscle specif ic enhancers, are bound by a family of transcription factors, MEF2A th rough -D, which are related to serum response factor in their DNA bind ing domains. We have found that MEF2D is the predominant protein in He La cells that binds to the c-jun MEF2 site. Serum induction of a MEF2 reporter gene was not observed in a line of NIH 3T3 cells which contai n low MEF2 site binding activity. Transfection of MEF2D into NIH 3T3 c ells reconstituted serum induction, demonstrating that MEF2D is requir ed for the serum response. Deletion analysis of MEF2D showed that its DNA binding domain, when fused to a heterologous transcriptional activ ation domain, was sufficient for serum induction of a MEF2 reporter ge ne. This is the domain homologous to that in the serum response factor which is required for serum induction of the c-fos serum response ele ment, suggesting that serum regulation of c-fos and c-jun may share a common mechanism.