A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.
The vitamin A derivative retinoic acid exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). We provide evidence that expression of the gene for cellular retinol-binding protein type II (CRBPII), a key protein in the intestinal absorption of vitamin A, is dramatically up-regulated by retinoic acid in the presence of RXR but not RAR. This regulation is conferred through a specific cis element in the CRBPII promoter that contains five nearly perfect tandem repeats of the sequence AGGTCA spaced by a single nucleotide. The discovery of this new RX response element provides a means for distinguishing between the two retinoid receptor systems and suggests that an RXR-mediated pathway exists for modulating vitamin A metabolism.
Mangelsdorf
D J
DJ
Howard Hughes Medical Institute, La Jolla, California 92186-5800.
Umesono
K
K
Kliewer
S A
SA
Borgmeyer
U
U
Ong
E S
ES
Evans
R M
RM
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid; D012045:Regulatory Sequences, Nucleic Acid; D012177:Retinol-Binding Proteins / Q000235:genetics*; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D014212:Tretinoin