NDLI: A Novel Intronic Peroxisome Proliferator-activated Receptor γ Enhancer in the Uncoupling Protein (UCP) 3 Gene as a Regulator of Both UCP2 and -3 Expression in Adipocytes*

Content Provider	PubMed Central
Author	Bugge, Anne Siersbæk, Majken Madsen, Maria S. Anita, Göndör Rougier, Carole Mandrup, Susanne
Abstract	Uncoupling Proteins (UCPs) are integral ion channels residing in the inner mitochondrial membrane. UCP2 is ubiquitously expressed, while UCP3 is found primarily in muscles and adipose tissue. Although the exact molecular mechanism of action is controversial, it is generally agreed that both homologues function to facilitate mitochondrial fatty acid oxidation. UCP2 and -3 expression is activated by the peroxisome proliferator-activated receptors (PPARs), but so far no PPAR response element has been reported in the vicinity of the Ucp2 and Ucp3 genes. Using genome-wide profiling of PPARγ occupancy in 3T3-L1 adipocytes we demonstrate that PPARγ associates with three chromosomal regions in the vicinity of the Ucp3 locus and weakly with a site in intron 1 of the Ucp2 gene. These sites are isolated from the nearest neighboring sites by >900 kb. The most prominent PPARγ binding site in the Ucp2 and Ucp3 loci is located in intron 1 of the Ucp3 gene and is the only site that facilitates PPARγ transactivation of a heterologous promoter. This site furthermore transactivates the endogenous Ucp3 promoter, and using chromatin conformation capture we show that it loops out to specifically interact with the Ucp2 promoter and intron 1. Our data indicate that PPARγ transactivation of both UCP2 and -3 is mediated through this novel enhancer in Ucp3 intron 1.
Related Links	http://dx.doi.org/10.1074/jbc.M110.120584
Starting Page	17310
File Format	PDF
ISSN	1083351X
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	23
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-06-04
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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A Novel Intronic Peroxisome Proliferator-activated Receptor γ Enhancer in the Uncoupling Protein (UCP) 3 Gene as a Regulator of Both UCP2 and -3 Expression in Adipocytes

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