The Myogenic Regulatory Factor MRF4 Represses the Cardiac α-Actin Promoter through a Negative-acting N-terminal Protein Domain

Cardiac α-actin is activated early during the development of embryonic skeletal muscle and cardiac myocytes. The gene product remains highly expressed in adult striated cardiac muscle yet is dramatically reduced in skeletal muscle. Activation and repression of cardiac α-actin gene activity in developing skeletal muscle correlates with changes in the relative content of the four myogenic regulatory factors. Cardiac α-actin promoter activity, assessed in primary chick myogenic cultures, was activated by endogenous myogenic regulatory factors but was inhibited in the presence of co-expressed MRF4. By exchanging N- and C-terminal domains of MRF4 and MyoD, the N terminus of MRF4 was identified as the mediator of repressive activity, revealing a novel negative regulatory role for MRF4. The relative ratios of myogenic regulatory factors may have fundamental roles in selecting specific muscle genes for activation and/or repression.