NUCLEAR PROTEINS THAT INTERACT WITH THE BETA(MAJ) GLOBIN PROMOTER START TO ACCUMULATE IN MEL CELLS WITHIN 12 HOURS OF INDUCTION AND RNA COPIES OF THE PROMOTER SUCCESSFULLY COMPETE THEIR BINDING IN-VITRO

The induction of differentiation in mouse erythroleukemia (MEL) cells by dimethylsulfoxide (DMSO) is characterized by increased transcriptio n of globin genes. We have determined that DMSO treated cells increase the levels of nuclear factors capable of overall interactions with th e beta(maj) globin promoter during the initial 24 h post induction, as measured by gel mobility analysis. Two unprocessed beta(maj) globin m RNA precursors, which are present in MEL cell nuclei early in differen tiation, were previously shown to contain the 5' promoter flanking reg ion, and thereby provided the nucleus with a pool of regulatory sequen ces in multiple RNA copies. We have studied the effect of RNA copies o f the promoter region on binding interactions between DNA sequences of the beta(maj) globin promoter and nuclear factors that interact with these sequences. The promoter region RNA transcripts competed effectiv ely for DNA binding proteins in vitro, while the antisense RNA from th e same region did not. The most pronounced competition was observed wi th proteins from 12 h after DMSO induction, when the concentration of the DNA binding proteins was still increasing. Since the 'upstream' tr anscripts predominate at 12 h after DMSO induction, these results indi cate that the promoter region transcripts may influence the equilibriu m of binding between the beta(maj) globin promoter and the nuclear fac tors that bind to this region during DMSO induction.