A MEF2 GENE THAT GENERATES A MUSCLE-SPECIFIC ISOFORM VIA ALTERNATIVE MESSENGER-RNA SPLICING

Members of the myocyte-specific enhancer-binding factor 2 (MEF2) famil y of transcription factors bind a conserved A/T-rich sequence in the c ontrol regions of numerous muscle-specific genes. Mammalian MEF2 prote ins have been shown previously to be encoded by three genes, Mef2, xMe f2, and Mef2c, each of which gives rise to multiple alternatively spli ced transcripts. We describe the cloning of a new member of the MEF2 f amily from mice, termed MEF2D, which shares extensive homology with ot her MEF2 proteins but is the product of a separate gene. MEF2D binds t o and activates transcription through the MEF2 site and forms heterodi mers with other members of the MEF2 family. Deletion mutations show th at the carboxyl terminus of MEF2D is required for efficient transactiv ation. MEF2D transcripts are widely expressed, but alternative splicin g of MEF2D transcripts gives rise to a muscle-specific isoform which i s induced during myoblast differentiation. The mouse Mef2, Mef2c, and Mef2d genes map to chromosomes 7, 13, and 3, respectively. The complex ity of the MEF2 family of regulatory proteins provides the potential f or fine-tuning of transcriptional responses as a consequence of combin atorial interactions among multiple MEF2 isoforms encoded by the four Mef2 genes.