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


Autoria(s): Juge-Aubry C.; Pernin A.; Favez T.; Burger A.G.; Wahli W.; Meier C.A.; Desvergne B.
Data(s)

01/10/1997

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_81B2299DBB2D

isbn:0021-9258[print], 0021-9258[linking]

pmid:9312141

doi:10.1074/jbc.272.40.25252

isiid:A1997XY97000080

Idioma(s)

en

Fonte

Journal of Biological Chemistry, vol. 272, no. 40, pp. 25252-25259

Palavras-Chave #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
Tipo

info:eu-repo/semantics/article

article