Abstract
We show here that the element which was previously characterized as a retinoid X receptor (RXR)-specific response element (RXRE) in the rat cellular retinol-binding protein II (CRBPII) gene is not conserved in the mouse gene. However, two conserved cis-acting elements (RE2 and RE3) located in the promoter region of the mouse and rat CRBPII genes mediate transactivation by retinoic acid receptors (RARs) and RXRs in transfected Cos-1, CV-1, and HeLa cells. The element RE3 which is the major retinoic acid (RA) response element also binds the transcription factors HNF-4 and ARP-1. HNF-4 constitutively activates the mouse CRBPII promoter, whereas ARP-1 represses the activation mediated by RARs, RXRs, and HNF-4. In contrast, RA has no effect on the activity of the mouse CRBPII promoter in the human colon carcinoma cell line CaCo-2 which constitutively expresses RAR alpha, RAR gamma, RXR alpha, HNF-4, and ARP-1, under conditions where the activity of the RAR beta 2 gene promoter is readily induced by RA. Our results suggest that the CRBPII gene may not be RA-inducible in tissues expressing HNF-4 and ARP-1, and that the RA inducibility of the CRBPII gene promoter observed in transfection experiments reflects the promiscuous binding of RARs/RXRs to HNF-4 and ARP-1 response elements.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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COUP Transcription Factor II
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COUP Transcription Factors
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DNA Primers / chemistry
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation*
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Hepatocyte Nuclear Factor 4
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphoproteins*
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Promoter Regions, Genetic
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RNA, Messenger / genetics
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Rats
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Retinoic Acid / metabolism*
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Receptors, Steroid*
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Retinoid X Receptors
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Retinol-Binding Proteins / genetics*
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Retinol-Binding Proteins, Cellular
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Sequence Alignment
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Sequence Homology, Nucleic Acid
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Structure-Activity Relationship
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transcriptional Activation
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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COUP Transcription Factor II
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COUP Transcription Factors
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DNA Primers
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DNA-Binding Proteins
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Hepatocyte Nuclear Factor 4
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Nr2f2 protein, mouse
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Nr2f2 protein, rat
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Phosphoproteins
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RBP2 protein, human
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RNA, Messenger
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Rbp2 protein, mouse
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Rbp2 protein, rat
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Steroid
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Retinoid X Receptors
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Retinol-Binding Proteins
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Retinol-Binding Proteins, Cellular
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Tcfl4 protein, mouse
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Transcription Factors
Associated data
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GENBANK/X74153
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GENBANK/X74154