mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
- 15 May 1994
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 8 (10), 1224-1234
- https://doi.org/10.1101/gad.8.10.1224
Abstract
Previously, we have isolated and characterized an enhancer from the 5'-flanking region of the adipocyte P2 (aP2) gene that directs high-level adipocyte-specific gene expression in both cultured cells and transgenic mice. The key regulator of this enhancer is a cell type-restricted nuclear factor termed ARF6. Target sequences for ARF6 in the aP2 enhancer exhibit homology to a direct repeat of hormone response elements (HREs) spaced by one nucleotide; this motif (DR-1) has been demonstrated previously to be the preferred binding site for heterodimers of the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR). We have cloned a novel member of the peroxisome proliferator-activated receptor family designated mPPAR gamma 2, and we demonstrate that a heterodimeric complex of mPPAR gamma 2 and RXR alpha constitute a functional ARF6 complex. Expression of mPPAR gamma 2 is induced very early during the differentiation of several cultured adipocyte cell lines and is strikingly adipose-specific in vivo. mPPAR gamma 2 and RXR alpha form heterodimers on ARF6-binding sites in vitro, and antiserum to RXR alpha specifically inhibits ARF6 activity in adipocyte nuclear extracts. Moreover, forced expression of mPPAR gamma 2 and RXR alpha activates the adipocyte-specific aP2 enhancer in cultured fibroblasts, and this activation is potentiated by peroxisome proliferators, fatty acids, and 9-cis retinoic acid. These results identify mPPAR gamma 2 as the first adipocyte-specific transcription factor and suggest mechanisms whereby fatty acids, peroxisome proliferators, 9-cis retinoic acid, and other lipids may regulate adipocyte gene expression and differentiation.Keywords
This publication has 33 references indexed in Scilit:
- Increase of adipose differentiation by hypolipidemic fibrate drugs in Ob 17 preadipocytes: Requirement for thyroid hormonesBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993
- Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation.Journal of Bone and Joint Surgery, 1992
- Homodimer formation of retinoid X receptor induced by 9-cis retinoic acidNature, 1992
- Reciprocal Regulation of Adipogenesis by Myc and C/EBPαScience, 1992
- Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptorsCell, 1992
- Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signallingNature, 1992
- Metabolic aspects of peroxisomal β-oxidationBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1991
- Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptorsCell, 1991
- Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferatorsNature, 1990
- Adipocyte conversion of cultured 3T3-Ll preadipocytes by bezafibrateLife Sciences, 1987