INHIBITION OF MYOGENIC BHLH AND MEF2 TRANSCRIPTION FACTORS BY THE BHLH PROTEIN TWIST

The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription fact ors are expressed in the myotome of developing somites and cooperative ly activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently exclud ed from the myotome. Ectopically expressed mouse Twist (Mtwist) was sh own to inhibit myogenesis by blocking DNA binding by MyoD, by titratin g E proteins, and by inhibiting trans-activation by MEF2. For inhibiti on of MEF2, Mtwist required heterodimerization with E proteins and an intact basic domain and carboxyl-terminus. Thus, Mtwist inhibits both families of myogenic regulators and may regulate myotome formation tem porally or spatially.