Characterization of a nuclear protein that interacts with regulatory elements in the human B creatine kinase gene

Abstract

The B creatine kinase gene is regulated by an array of positive and negative cis-elements in the 5'-flanking DNA that function in both muscle 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 between -92 and +80 of the B creatine kinase gene confer a regulated pattern of expression to chimeric plasmids that closely resembles the time course of expression of the endogenous B creatine kinase gene in C2C12 cells undergoing differentiation. We show that sequences within the first exon of the B creatine kinase gene are important for the developmental regulation of the gene in C2C12 cells and that these sequences bind a nuclear protein that shows a similar tissue- specific distribution and developmentally regulated expression to that of the endogenous B creatine kinase gene.