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.
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.
Helledie
Torben
T
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense University, Campusvej 55, 5230 Odense M, Denmark.
Grøntved
Lars
L
Jensen
Søren S
SS
Kiilerich
Pia
P
Rietveld
Luc
L
Albrektsen
Tatjana
T
Boysen
Maria S
MS
Nøhr
Jane
J
Larsen
Leif K
LK
Fleckner
Jan
J
Stunnenberg
Hendrik G
HG
Kristiansen
Karsten
K
Mandrup
Susanne
S
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007438:Introns; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D003432:Cross-Linking Reagents; D026261:Diazepam Binding Inhibitor; D005343:Fibrinolytic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; C089946:2,4-thiazolidinedione