The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers

Harikrishna Nakshatri, Pierre Chambon

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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 trans- activation 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 RARα, RARγ, RXRα, HNF-4, and ARP-1, under conditions where the activity of the RARβ2 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.

Original languageEnglish (US)
Pages (from-to)890-902
Number of pages13
JournalJournal of Biological Chemistry
Volume269
Issue number2
StatePublished - Jan 14 1994
Externally publishedYes

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Cellular Retinol-Binding Proteins
Retinoid X Receptors
Retinoic Acid Receptors
Tretinoin
Rats
Genes
Binding Sites
Response Elements
Chemical activation
HeLa Cells
Genetic Promoter Regions
Transfection
Colon
Transcription Factors
Cells
Tissue
Carcinoma
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers",
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 trans- activation 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 RARα, RARγ, RXRα, HNF-4, and ARP-1, under conditions where the activity of the RARβ2 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.",
author = "Harikrishna Nakshatri and Pierre Chambon",
year = "1994",
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T1 - The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers

AU - Nakshatri, Harikrishna

AU - Chambon, Pierre

PY - 1994/1/14

Y1 - 1994/1/14

N2 - 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 trans- activation 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 RARα, RARγ, RXRα, HNF-4, and ARP-1, under conditions where the activity of the RARβ2 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.

AB - 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 trans- activation 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 RARα, RARγ, RXRα, HNF-4, and ARP-1, under conditions where the activity of the RARβ2 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.

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