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Originally published In Press as doi:10.1074/jbc.M005713200 on August 24, 2000

J. Biol. Chem., Vol. 275, Issue 46, 36394-36399, November 17, 2000
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The Uncoupling Protein-3 Gene Is Transcribed from Tissue-specific Promoters in Humans but Not in Rodents*

Harald EsterbauerDagger , Hannes OberkoflerDagger , Franz Krempler§, A. Donny Strosberg, and Wolfgang PatschDagger ||

From the Dagger  Department of Laboratory Medicine, Landeskliniken Salzburg, A-5020 Austria, the § Department of Internal Medicine, Krankenhaus Hallein, A-5400 Austria, and the  Institute Cochin de Genetique Moleculaire, Paris, 75014 France

Uncoupling protein-3 (UCP3), a mitochondrial membrane transporter, is a candidate effector of thermogenesis. Even though mice with targeted disruption of the UCP3 gene are not obese, indirect evidence suggests that this protein contributes to the control of energy expenditure in humans. We therefore characterized the human UCP3 gene and compared it with its rodent homologues with respect to tissue-specific expression and regulatory regions. Like rodent UCP3, human UCP3 was expressed in skeletal muscle and brown adipose tissue (BAT). The short mRNA isoform, UCP3S, which is absent in rodents, was relatively more abundant in human skeletal muscle in comparison to human BAT. Two tissue-specific transcription start sites for each skeletal muscle and BAT were delineated for human UCP3. Tissue-specific transcript initiation was maintained in both tissues and cultured cells over a wide range of expression levels. In contrast, rodent transcripts were initiated at the same site in BAT and muscle tissue. Comparison of human and rodent promoters indicated a rapid phylogenetic evolution suggesting functional diversification. The transcription from tissue-specific promoters in humans is a novel finding that may provide the basis for therapeutic interventions aimed at regulating energy expenditure in a tissue-specific fashion.

* This work was supported by a grant from the Medizinische Forschungsgesellschaft Salzburg and the Stiftung Propter Homines, Vaduz, Liechtenstein.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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF050113 and AF168989.

|| To whom correspondence should be addressed: Dept. of Laboratory Medicine, Landeskliniken Salzburg, A-5020 Salzburg, Austria. Tel.: 43-662-4482-3800; Fax: 43-662-4482-885; E-mail: w.patsch@lks.at.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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