A new serum-responsive, cardiac tissue-specific transcription factor that recognizes the MEF-2 site in the myosin light chain-2 promoter.
We have identified a serum-responsive, cardiac tissue-specific transcription factor, BBF-1, that recognizes an AT-rich sequence (element B), identical to the myocyte enhancer factor (MEF-2) target site, in the cardiac myosin light chain-2 (MLC-2) promoter. Deletion of the element B sequence alone from the cardiac MLC-2 promoter causes, as does that of the MEF-2 site from other promoters and the enhancer of skeletal muscle genes, a marked reduction of transcription. BBF-1 is distinguishable from cardiac MEF-2 on the basis of immunoprecipitation with an antibody which recognizes MEF-2 but not BBF-1. Unlike MEF-2, BBF-1 is present exclusively in nuclear extracts from cardiac muscle cells cultured in a medium containing a high concentration of serum. Removal of serum from culture medium abolishes BBF-1 activity selectively with a concomitant loss of the positive regulatory effect of element B on MLC-2 gene transcription, indicating that there is a correlation between the BBF-1 binding activity and the tissue-specific role of the element B (MEF-2 site) sequence. The loss of element B-mediated activation of transcription is reversed following the refeeding of cells with serum-containing medium. These data demonstrate that cardiac muscle cells contain two distinct protein factors, MEF-2 and BBF-1, which bind to the same target site but that, unlike MEF-2, BBF-1 is serum inducible and cardiac tissue specific. BBF-1 thus appears to be a crucial member of the MEF-2 family of proteins which will serve as an important tool in understanding the regulatory mechanism(s) underlying cardiogenic differentiation.
Zhou
M D
MD
Department of Anatomy and Cell Biology, State University of New York Health Science Center, Brooklyn 11203.
Goswami
S K
SK
Martin
M E
ME
Siddiqui
M A
MA
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D001769:Blood; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D009218:Myosins / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D004247:DNA; D009218:Myosins