This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boyer, B B Articles by Kozak, L P Search for Related Content PubMed PubMed Citation Articles by Boyer, B B Articles by Kozak, L P

The mitochondrial uncoupling protein gene in brown fat: correlation between DNase I hypersensitivity and expression in transgenic mice.

Jackson Laboratory, Bar Harbor, Maine 04609.

ABSTRACT

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA. Transgenic mice with an uncoupling protein minigene were generated by microinjection of fertilized eggs with a transgene containing 3 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. Expression of the transgene is restricted to brown fat and is cold inducible. Four additional transgenic lines were generated with a second transgene containing a 1.8-kb deletion in the 5'-flanking DNA, and expression of this minigene is absent in all tissues analyzed. A DNase I-hypersensitive site located in the 1.8-kb deletion contains a cyclic AMP response element that binds a brown fat tumor enriched nuclear factor. On the basis of these observations, we propose that a cis-acting regulatory sequence between -3 and -1.2 kb of the 5'-flanking region, possibly at a DNase I-hypersensitive site, is required for controlling uncoupling protein expression in vivo.

This article has been cited by other articles:

• Kramarova, T. V., Shabalina, I. G., Andersson, U., Westerberg, R., Carlberg, I., Houstek, J., Nedergaard, J., Cannon, B. (2008). Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c-Fo subunit P1 isoform. FASEB J. 22: 55-63 [Abstract] [Full Text]  
• Frontini, A., Rousset, S., Cassard-Doulcier, A.-M., Zingaretti, C., Ricquier, D., Cinti, S. (2007). Thymus Uncoupling Protein 1 Is Exclusive to Typical Brown Adipocytes and Is Not Found in Thymocytes. J. Histochem. Cytochem. 55: 183-189 [Abstract] [Full Text]  
• Rim, J. S., Kozak, L. P. (2002). Regulatory Motifs for CREB-binding Protein and Nfe2l2 Transcription Factors in the Upstream Enhancer of the Mitochondrial Uncoupling Protein 1 Gene. J. Biol. Chem. 277: 34589-34600 [Abstract] [Full Text]  
• Valet, P., Tavernier, G., Castan-Laurell, I., Saulnier-Blache, J. S., Langin, D. (2002). Understanding adipose tissue development from transgenic animal models. J. Lipid Res. 43: 835-860 [Abstract] [Full Text]  
• Cittadini, A., Mantzoros, C. S., Hampton, T. G., Travers, K. E., Katz, S. E., Morgan, J. P., Flier, J. S., Douglas, P. S. (1999). Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat : An Animal Model of Human Obesity. Circulation 100: 2177-2183 [Abstract] [Full Text]  
• Boyer, B. B., Barnes, B. M., Lowell, B. B., Grujic, D. (1998). Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Am. J. Physiol. Regul. Integr. Comp. Physiol. 275: R1232-R1238 [Abstract] [Full Text]  
• Yubero, P., Barberá, M., Alvarez, R., Viñas, O., Mampel, T., Iglesias, R., Villarroya, F., Giralt, M. (1998). Dominant Negative Regulation by c-Jun of Transcription of the Uncoupling Protein-1 Gene through a Proximal cAMP-Regulatory Element: A Mechanism for Repressing Basal and Norepinephrine-Induced Expression of the Gene before Brown Adipocyte Differentiation. Mol. Endocrinol. 12: 1023-1037 [Abstract] [Full Text]  
• Mason, M. M., He, Y., Chen, H., Quon, M. J., Reitman, M. (1998). Regulation of Leptin Promoter Function by Sp1, C/EBP, and a Novel Factor. Endocrinology 139: 1013-1022 [Abstract] [Full Text]  
• Przyborski, S., Knowles, B., Ackerman, S. (1998). Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during the formation of the rostral cerebellar boundary. Development 125: 41-50 [Abstract]  
• Urhammer, S. A., Fridberg, M., Sorensen, T. I. A., Echwald, S. M., Andersen, T., Tybjarg-Hansen, A., Clausen, J. O., Pedersen, O. (1997). Studies of Genetic Variability of the Uncoupling Protein 1 Gene in Caucasian Subjects with Juvenile-Onset Obesity. J. Clin. Endocrinol. Metab. 82: 4069-4074 [Abstract] [Full Text]  
• Rabelo, R., Camirand, A., Silva, J. E. (1997). 3',5'-Cyclic Adenosine Monophosphate-Response Sequences of the Uncoupling Protein Gene Are Sequentially Recruited During Darglitazone-Induced Brown Adipocyte Differentiation. Endocrinology 138: 5325-5332 [Abstract] [Full Text]  
• Grujic, D., Susulic, V. S., Harper, M.-E., Himms-Hagen, J., Cunningham, B. A., Corkey, B. E., Lowell, B. B. (1997). beta 3-Adrenergic Receptors on White and Brown Adipocytes Mediate beta 3-Selective Agonist-induced Effects on Energy Expenditure, Insulin Secretion, and Food Intake. A STUDY USING TRANSGENIC AND GENE KNOCKOUT MICE. J. Biol. Chem. 272: 17686-17693 [Abstract] [Full Text]  
• Larose, M., Cassard-Doulcier, A.-M., Fleury, C., Serra, F., Champigny, O., Bouillaud, F., Ricquier, D. (1996). Essential cis-Acting Elements in Rat Uncoupling Protein Gene Are in an Enhancer Containing a Complex Retinoic Acid Response Domain. J. Biol. Chem. 271: 31533-31542 [Abstract] [Full Text]  
• Kozak, L P, Kozak, U C, Clarke, G T (1991). Abnormal brown and white fat development in transgenic mice overexpressing glycerol 3-phosphate dehydrogenase.. Genes Dev. 5: 2256-2264 [Abstract]