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PMID: 9580705 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Multiple parameters determine the specificity of transcriptional response by nuclear receptors HNF-4, ARP-1, PPAR, RAR and RXR through common response elements.

Nucleic acids research ·Vol. 26 ·No. 10 ·1998-05-15 ·Pages 2491-9

Nakshatri H, Bhat-Nakshatri P

Abstract

A number of nuclear receptors, including retinoic acid receptors (RARs), retinoid-X receptors (RXRs), hepatocyte nuclear factor 4 (HNF-4), chicken ovalbumin upstream promoter transcription factor I (COUP-TFI), apolipoprotein regulatory protein 1 (ARP-1) and peroxisome proliferator-activated receptor (PPAR), bind to response elements comprised of two core motifs, 5'-RG(G/T)TCA, or a closely related sequence separated by 1 nt (DR1 elements). The potential role of the precise sequence of the core motif as well as the spacer nucleotide in determining specificity and promiscuity of receptor-response element interactions was investigated. We show here that nucleotides at base positions 1, 2 and 4 of the core motif as well as the spacer nucleotide determine the binding preference of HNF-4 and ARP-1 homodimers and RAR:RXR and PPAR:RXR heterodimers. In transfection experiments transcriptional activation by HNF-4 and PPAR:RXR and repression by ARP-1 correlated with the relative in vitro binding affinity provided the element was located within the proper promoter context. Furthermore, promoter context also determined whether an element that binds to HNF-4 and PPAR:RXR with equal affinity functions as an HNF-4 response element or PPAR response element. Thus, apart from the element-specific differences in affinity for the receptors, additional promoter-specific transcription factors that interact with HNF-4 and PPAR:RXR determine the specificity of transcriptional response through DR1-type elements.

MeSH Terms
Animals Base Sequence COS Cells Cell Line DNA/metabolism Dimerization Haplorhini Mice Promoter Regions, Genetic/genetics Protein Binding Rats Receptors, Cytoplasmic and Nuclear/metabolism Recombinant Fusion Proteins Regulatory Sequences, Nucleic Acid/genetics Repetitive Sequences, Nucleic Acid/genetics Transcription Factors/metabolism Transcriptional Activation/genetics
Chemicals
Receptors, Cytoplasmic and Nuclear Recombinant Fusion Proteins Transcription Factors DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nakshatri H
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. hnakshat@iupui.edu
Bhat-Nakshatri P
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/26.10.2491
Email
hnakshat@iupui.edu
Published
1998-05-15
Pages
2491-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC147560
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/26.10.2491 PMC Full Text View journal details
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