The myogenic regulatory factor MRF4 represses the cardiac alpha-actin promoter through a negative-acting N-terminal protein domain.
Cardiac alpha-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 alpha-actin gene activity in developing skeletal muscle correlates with changes in the relative content of the four myogenic regulatory factors. Cardiac alpha-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.
Moss
J B
JB
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA. moss@helix.mgh.harvard.edu
Olson
E N
EN
Schwartz
R J
RJ
D000199:Actins / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
D000199:Actins; D017570:MyoD Protein; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D014157:Transcription Factors; C063403:myogenic factor 6