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Identification of an extended half‐site motif required for the function of peroxisome proliferator‐activated receptor α
Author(s) -
Osada Shiho,
Tsukamoto Toshiro,
Takiguchi Masaki,
Mori Masataka,
Osumi Takashi
Publication year - 1997
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1997.1220319.x
Subject(s) - retinoid x receptor , biology , nuclear receptor , peroxisome , peroxisome proliferator activated receptor , binding site , biochemistry , peroxisome proliferator activated receptor alpha , enhancer , receptor , consensus sequence , transcription factor , sequence motif , gene , microbiology and biotechnology , peptide sequence
Background: Peroxisome proliferator‐activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and regulate many genes of the proteins involved in lipid metabolism, including peroxisomal acyl‐CoA oxidase (AOX). Through heterodimerization with retinoid X receptors (RXRs), PPAR was believed to recognize the sequence elements consisting of two directly repeating 6‐bp half‐sites spaced by one nucleotide (DR‐1), located in the regulatory regions of these genes. Results: Employing the peroxisome proliferator‐responsive enhancer of the rat AOX gene, we analysed the minimal sequence requirements for enhancer activity and PPARα/RXRα binding. We found that the sequence just downstream of the DR‐1 motif is indispensable for both functions. By a direct selection procedure of high‐affinity binding sites from a random sequence pool, we identified a consensus sequence at the four positions next to DR‐1. We also suggest that PPARα binds to the downstream half‐site, whereas RXRα binds to the upstream half‐site of the AOX DR‐1. Conclusions: An extended half‐site of 10‐bp, but not a simple 6‐bp half‐site, is required for the PPARα binding, upon heterodimer formation with RXRα. The binding polarity of PPARα/RXRα seems to be opposite to that of other RXR‐involving heterodimers.