CLONING AND FUNCTIONAL-CHARACTERIZATION OF LCR-F1 - A BZIP TRANSCRIPTION FACTOR THAT ACTIVATES ERYTHROID-SPECIFIC, HUMAN GLOBIN GENE-EXPRESSION

DNase I hypersensitive site 2 (HS 2) of the human beta-globin Locus Co ntrol Region (LCR) directs high level expression of the beta-globin ge ne located 50 kilobases downstream. Experiments in cultured cells and in transgenic mice demonstrate that duplicated AP1-like sites in HS 2 are required for this powerful enhancer activity. A cDNA clone encodin g a basic, leucine-zipper protein that binds to these sites was isolat ed and designated Locus Control Region-Factor 1 (LCR-F1). This protein is a member of a new family of regulatory factors that contain a 63 a mino acid 'CNC domain' overlapping the basic region. This domain is ap proximately 70% identical in the Drosophila Cap N Collar (CNC) protein , NF-E2 and LCR-F1. LCR-F1 transactivates an HS 2/gamma-globin reporte r gene over 170-fold in transient transfection experiments specificall y in erythroid cells. These results suggest that LCR-F1 may be a criti cal factor involved in LCR-mediated, human globin gene expression.