A NOVEL, TISSUE-RESTRICTED ZINC-FINGER PROTEIN (HF-1B) BINDS TO THE CARDIAC REGULATORY ELEMENT (HF-1B MEF-2) IN THE RAT MYOSIN LIGHT-CHAIN 2 GENE/

The AT-rich element MEF-2 plays an important role in the maintenance o f the muscle-specific expression of a number of cardiac and skeletal m uscle genes. In the MLC-2 gene, an AT-rich element (HF-1b) which conta ins a consensus MEF-2 site is required for cardiac tissue-specific exp ression. The present study reports the isolation and characterization of a cDNA which encodes a novel C2H2 zinc finger (HF-1b) that binds in a sequence-specific manner to the HF-1b/MEF-2 site in the MLC-2 promo ter. A number of independent criteria suggest that this HF-1b zinc fin ger protein is a component of the endogenous HF-1b/MEF-2 binding activ ity in cardiac muscle cells and that it can serve as a transcriptional activator of the MLC-2 promoter in transient assays. These studies su ggest that, in addition to the previously reported RSRF proteins, stru cturally divergent transcriptional factors can bind to MEF-2-like site s in muscle promoters. These results underscore the complexity of the regulation of the muscle gene program via these AT-rich elements in ca rdiac and skeletal muscle.