DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.

Détails

ID Serval
serval:BIB_81B2299DBB2D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.
Périodique
Journal of Biological Chemistry
Auteur(s)
Juge-Aubry C., Pernin A., Favez T., Burger A.G., Wahli W., Meier C.A., Desvergne B.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
10/1997
Volume
272
Numéro
40
Pages
25252-25259
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The three subtypes of the peroxisome proliferator-activated receptors (PPARalpha, beta/delta, and gamma) form heterodimers with the 9-cis-retinoic acid receptor (RXR) and bind to a common consensus response element, which consists of a direct repeat of two hexanucleotides spaced by one nucleotide (DR1). As a first step toward understanding the molecular mechanisms determining PPAR subtype specificity, we evaluated by electrophoretic mobility shift assays the binding properties of the three PPAR subtypes, in association with either RXRalpha or RXRgamma, on 16 natural PPAR response elements (PPREs). The main results are as follows. (i) PPARgamma in combination with either RXRalpha or RXRgamma binds more strongly than PPARalpha or PPARbeta to all natural PPREs tested. (ii) The binding of PPAR to strong elements is reinforced if the heterodimerization partner is RXRgamma. In contrast, weak elements favor RXRalpha as heterodimerization partner. (iii) The ordering of the 16 natural PPREs from strong to weak elements does not depend on the core DR1 sequence, which has a relatively uniform degree of conservation, but correlates with the number of identities of the 5'-flanking nucleotides with respect to a consensus element. This 5'-flanking sequence is essential for PPARalpha binding and thus contributes to subtype specificity. As a demonstration of this, the PPARgamma-specific element ARE6 PPRE is able to bind PPARalpha only if its 5'-flanking region is exchanged with that of the more promiscuous HMG PPRE.
Mots-clé
3T3 Cells, Animals, Base Sequence, Binding Sites, Chloramphenicol O-Acetyltransferase/biosynthesis, Consensus Sequence, DNA-Binding Proteins/biosynthesis, DNA-Binding Proteins/chemistry, Dimerization, Genes, Reporter, Humans, Mice, Protein Biosynthesis, Rabbits, Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Receptors, Pituitary Hormone/biosynthesis, Receptors, Pituitary Hormone/chemistry, Receptors, Retinoic Acid/biosynthesis, Receptors, Retinoic Acid/chemistry, Recombinant Proteins/biosynthesis, Recombinant Proteins/chemistry, Repetitive Sequences, Nucleic Acid, Retinoid X Receptors, Sequence Alignment, Substrate Specificity, Transcription Factors/biosynthesis, Transcription Factors/chemistry, Transcription, Genetic, Transfection, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:27
Dernière modification de la notice
08/05/2019 21:10
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