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Originally published In Press as doi:10.1074/jbc.M111295200 on May 15, 2002

J. Biol. Chem., Vol. 277, Issue 30, 26821-26830, July 26, 2002
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The Gene Encoding the Acyl-CoA-binding Protein Is Activated by Peroxisome Proliferator-activated Receptor gamma  through an Intronic Response Element Functionally Conserved between Humans and Rodents*

Torben Helledie, Lars Grøntved, Søren S. Jensen, Pia Kiilerich, Luc RietveldDagger , Tatjana Albrektsen§, Maria S. Boysen, Jane Nøhr, Leif K. Larsen, Jan Fleckner§, Hendrik G. StunnenbergDagger , Karsten Kristiansen, and Susanne Mandrup

From the Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark, the Dagger  Department of Molecular Biology, Nijmegen Center for Molecular Life Sciences, 6525 GA Nijmegen, The Netherlands, and § Novo, Nordisk A/S, 2880 Bagsvoerd, Denmark

The acyl-CoA-binding protein (ACBP) is a 10-kDa intracellular protein that specifically binds acyl-CoA esters with high affinity and is structurally and functionally conserved from yeast to mammals. In vitro studies indicate that ACBP may regulate the availability of acyl-CoA esters for various metabolic and regulatory purposes. The protein is particularly abundant in cells with a high level of lipogenesis and de novo fatty acid synthesis and is significantly induced during adipocyte differentiation. However, the molecular mechanisms underlying the regulation of ACBP expression in mammalian cells have remained largely unknown. Here we report that ACBP is a novel peroxisome proliferator-activated receptor (PPAR)gamma target gene. The rat ACBP gene is directly activated by PPARgamma /retinoid X receptor alpha  (RXRalpha ) and PPARalpha /RXRalpha , but not by PPARdelta /RXRalpha , through a PPAR-response element in intron 1, which is functionally conserved in the human ACBP gene. The intronic PPAR-response element (PPRE) mediates induction by endogenous PPARgamma in murine adipocytes and confers responsiveness to the PPARgamma -selective ligand BRL49653. Finally, we have used chromatin immunoprecipitation to demonstrate that the intronic PPRE efficiently binds PPARgamma /RXR in its natural chromatin context in adipocytes. Thus, the PPRE in intron 1 of the ACBP gene is a bona fide PPARgamma -response element.

* This work was supported by the Danish Natural Science Research Council.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, University of Southern Denmark, Odense University, Campusvej 55, 5230 Odense M, Denmark, Tel.: 45-6550- 2340; Fax: 45-6550-2467; E-mail: s.mandrup@bmb.sdu.dk.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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