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 Rietveld, Tatjana Albrektsen, Maria S Boysen, Jane Nøhr, Leif K Larsen, Jan Fleckner, Hendrik G Stunnenberg, Karsten Kristiansen, Susanne Mandrup

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume277
Issue number30
Pages (from-to)26821-30
ISSN0021-9258
DOIs
Publication statusPublished - 2002

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Diazepam Binding Inhibitor
Gene encoding
PPAR gamma
Response Elements
Rodentia
Peroxisome Proliferator-Activated Receptors
Retinoid X Receptor alpha
Genes
Adipocytes
Acyl Coenzyme A
rosiglitazone
Introns
Chromatin
Esters
PPAR delta
PPAR alpha
Lipogenesis
Mammals
Chromatin Immunoprecipitation
Yeast

Cite this

Helledie, Torben ; Grøntved, Lars ; Jensen, Søren S ; Kiilerich, Pia ; Rietveld, Luc ; Albrektsen, Tatjana ; Boysen, Maria S ; Nøhr, Jane ; Larsen, Leif K ; Fleckner, Jan ; Stunnenberg, Hendrik G ; Kristiansen, Karsten ; Mandrup, Susanne. / 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. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 30. pp. 26821-30.
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title = "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.",
abstract = "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.",
author = "Torben Helledie and Lars Gr{\o}ntved and Jensen, {S{\o}ren S} and Pia Kiilerich and Luc Rietveld and Tatjana Albrektsen and Boysen, {Maria S} and Jane N{\o}hr and Larsen, {Leif K} and Jan Fleckner and Stunnenberg, {Hendrik G} and Karsten Kristiansen and Susanne Mandrup",
year = "2002",
doi = "10.1074/jbc.M111295200",
language = "English",
volume = "277",
pages = "26821--30",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
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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. / Helledie, Torben; Grøntved, Lars; Jensen, Søren S; Kiilerich, Pia; Rietveld, Luc; Albrektsen, Tatjana; Boysen, Maria S; Nøhr, Jane; Larsen, Leif K; Fleckner, Jan; Stunnenberg, Hendrik G; Kristiansen, Karsten; Mandrup, Susanne.

In: Journal of Biological Chemistry, Vol. 277, No. 30, 2002, p. 26821-30.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 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.

AU - Helledie, Torben

AU - Grøntved, Lars

AU - Jensen, Søren S

AU - Kiilerich, Pia

AU - Rietveld, Luc

AU - Albrektsen, Tatjana

AU - Boysen, Maria S

AU - Nøhr, Jane

AU - Larsen, Leif K

AU - Fleckner, Jan

AU - Stunnenberg, Hendrik G

AU - Kristiansen, Karsten

AU - Mandrup, Susanne

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M111295200

DO - 10.1074/jbc.M111295200

M3 - Journal article

C2 - 12015306

VL - 277

SP - 26821

EP - 26830

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -