A DNA-BENDING PROTEIN INTERACTS WITH AN ESSENTIAL UPSTREAM REGULATORYELEMENT OF THE HUMAN EMBRYONIC BETA-LIKE GLOBIN GENE

The mammalian beta-like globin gene family has served as an important model system for analysis of tissue- and developmental stage-specific gene regulation, Although the activities of a number of regulatory pro teins have been implicated in the erythroid cell-specific transcriptio n of globin genes, the mechanisms that restrict their expression to di screte stages of development are less well understood, We have previou sly identified a novel regulatory element (PRE II) upstream from the h uman embryonic beta-like globin gene (epsilon) that synergizes with ot her sequences to confer tissue- and stage-specific expression on a min imal epsilon-globin gene promoter in cultured embryonic erythroid cell s. Binding of an erythroid nuclear protein (PRE II-binding factor [PRE IIBF]) to the PRE II control element is required for promoter activati on. Here we report on some of the biochemical properties of PREIIBF, i ncluding the characterization of its specificity and affinity for DNA, The embryonic and adult forms of PREIIBF recognize their cognate sequ ences with identical specificities, supporting our earlier conclusion that they are very similar proteins. PREIIBF binds DNA as a single pol ypeptide with an M(r) of similar to 80000 to 85000 and introduces a be nd into the target DNA molecule. These results suggest a mechanism by which PREIIBF may contribute to the regulation of the embryonic beta-l ike globin gene within the context of a complex locus.