Identification of a retinoid receptor response element in the human aldehyde dehydrogenase-2 promoter.
BACKGROUND
The human aldehyde dehydrogenase-2 promoter contains sites that bind members of the nuclear receptor family, and one (designated FP330-3') is predicted to bind retinoic acid receptors.


METHODS
Binding of retinoid receptors to the FP330-3' oligonucleotide duplex and point mutations thereof was assayed using electrophoretic mobility shift assays. The function of the promoter element was determined in transfection assays.


RESULTS
Heterodimers of retinoic acid receptor (RAR)alpha, beta, and gamma with retinoid X receptor (RXR)alpha bound the FP330-3' site. Mutagenesis of the FP330-3' site suggested that either the upstream DR-5 or downstream DR-1 could mediate binding of RAR/RXR. FP330-3' oligonucleotide duplexes were not bound by in vitro translated RXR homodimers but weakly competed with a synthetic DR-1 oligonucleotide duplex for binding by RXR. A reporter construct carrying four copies of the FP330-3' element was induced by cotransfection of rat hepatoma cells with a construct encoding RARalpha, when the RAR-specific ligand AM580 was present. Each of the three RXR isoforms alpha, beta, and gamma stimulated the expression of reporter constructs containing the FP330-3' sites in a 9-cis retinoic acid-dependent fashion in cells in culture. This was confirmed in the case of RXRalpha using the RXR-specific ligand methoprene.


CONCLUSIONS
The human aldehyde dehydrogenase-2 promoter contains a retinoid response element, which may contribute to regulation of the gene.
Pinaire
Jane
J
Department of Medicine, Indiana University School of Medicine and Veterans Affairs Medical Center, Indianapolis, USA.
Chou
Wan-Yin
WY
Morton
Michael
M
You
Min
M
Zeng
Yan
Y
Cho
Won Kyoo
WK
Galli
Andrea
A
Everett
Lynn
L
Breen
Heather
H
Dumaual
Natividad
N
Smith
Jennifer R
JR
Crabb
David
D
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002460:Cell Line; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma
D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607073:Rara protein, rat; C082925:retinoic acid receptor beta; C096127:ALDH2 protein, human