CHARACTERIZATION OF A NUCLEAR-PROTEIN THAT INTERACTS WITH REGULATORY ELEMENTS IN THE HUMAN B-CREATINE-KINASE GENE

The B creatine kinase gene is regulated by an array of positive and ne gative cis-elements in the 5'-flanking DNA that function in both muscl e and nonmuscle cells. In C2C12 myogenic cells M and B creatine kinase mRNAs are coordinately up-regulated in the early stages of myogenesis and then undergo distinct regulatory programs. The B creatine kinase gene is down-regulated in the late stages of myogenesis as M creatine kinase becomes the predominant species in mature myotubes, Sequences b etween -92 and +80 of the B creatine kinase gene confer a regulated pa ttern of expression to chimeric plasmids that closely resembles the ti me course of expression of the endogenous B creatine kinase gene in C2 C12 cells undergoing differentiation. We show that sequences within th e first exon of the B creatine kinase gene are important for the devel opmental regulation of the gene in C2C12 cells and that these sequence s bind a nuclear protein that shows a similar tissue-specific distribu tion and developmentally regulated expression to that of the endogenou s B creatine kinase gene.