Nucleic Acids Research, 1994, Vol. 22, No. 12 2383-2391
© 1994
MOLECULAR BIOLOGY |
Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham Birmingham, AL 35294, USA
*To whom correspondence should be addressed
Received February 2, 1994. Revised May 12, 1994. Accepted May 12, 1994.
DNase I hypersensitive site 2 (HS 2) of the human ß-globin Locus Control Region (LCR) directs high level expression of the ß-globin gene 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 encoding a basic, leucine-zipper protein that binds to these sites was isolated 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 amino acid ‘CNC domain’ overlapping the basic region. This domain is approximately 70% identical in the Drosophila Cap N Collar (CNC) protein, NF-E2 and LCR-F1. LCR-F1 transactivates an HS 2/
-globin reporter gene over 170-fold in transient transfection experiments specifically in erythroid cells. These results suggest that LCR-F1 may be a critical factor involved in LCR-mediated, human globin gene expression.
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