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Characterization of a Retinoic Acid Responsive Element in the Human ets‐1 Promoter
Author(s) -
So Eddie N.,
Crowe David L.
Publication year - 2000
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/713803742
Subject(s) - retinoic acid , transactivation , retinoic acid receptor , response element , promoter , retinoic acid inducible orphan g protein coupled receptor , retinoic acid receptor gamma , transcription factor , biology , retinoic acid receptor beta , transcription (linguistics) , electrophoretic mobility shift assay , microbiology and biotechnology , retinoid x receptor , gene , gene expression , regulation of gene expression , retinoic acid receptor alpha , chemistry , biochemistry , nuclear receptor , linguistics , philosophy
The vitamin A metabolite retinoic acid (RA) is a powerful regulator of cellular proliferation and differentiation. The effects of RA on target gene expression are mediated by a family of ligand dependent nuclear transcription factors known as retinoic acid receptors (RAR). RARs have functional domains for retinoic acid binding, dimerization, and transactivation. RA response elements (RARE) found in the promoters of many genes consist of variable direct repeats of the sequence PuGGTCA spaced by five nucleotides (DR5). We have identified a novel DR5 element in the human ets-1 promoter. Mutational analysis of this site indicates that it is necessary for RA- and RAR-dependent activation of the ets-1 promoter. RARalpha can bind specifically to this site as determined by electrophoretic mobility shift analysis. Finally, RA mediates induction of the human ets-1 gene at the mRNA and protein levels. These data suggest that induction of ets-1 expression by RA is mediated by a novel retinoic acid response element in the promoter region of this gene.