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Cited by 2,181

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.

Open access
Tontonoz, P, Hu, E, Graves, R A, Budavari, A I, Spiegelman, B M·1994·Genes & Development
DOI 10.1101/gad.8.10.1224
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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.

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Metadata

Authors
Tontonoz, P., Hu, E., Graves, R. A., Budavari, A. I., & Spiegelman, B. M.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
1994-05-15
Volume
8
Issue
10
Pages
1224-1234
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.8.10.1224
OpenAlex
W2164015929
Cited by
2,181
References
2
Type
posted content
Language
en
Open access
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