Volume 271, Number 49, Issue of December 6, 1996 pp. 31533-31542
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Essential cis-Acting Elements in Rat Uncoupling Protein Gene Are in an Enhancer Containing a Complex Retinoic Acid Response Domain

(Received for publication, February 26, 1996, and in revised form, August 26, 1996)

From the Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique, 92190 Meudon, France

Transgenic mice were generated with a transgene containing the 211-base pair (bp) enhancer and 0.4 kilobase pairs of 5-flanking DNA of the uncoupling protein (ucp) gene. Expression of this transgene was restricted to brown adipose tissue and was inducible by cold exposure or treatment of transgenic mice by norepinephrine, retinoic acid (RA), or CL-316,243 3-adrenoreceptor agonist. A search for retinoic acid response elements in the ucp gene enhancer was undertaken using mutagenesis and transfection of cultured cells with chloramphenicol acetyltransferase constructs. Deletion or mutations of several putative retinoic acid response elements were ineffective. Mutations of a TGAATCA region dramatically decreased the transcriptional activity in the presence of RA. In vitro this region was able to bind a complex containing proteins recognized by antibodies against Jun or Fos. Mutations of an adjacent region related to an inverted repeat of type 2 also markedly decreased RA effect. This region was able to bind in vitro retinoid X receptor  and retinoic acid receptor . The two regions form an activating region between bp 2421 and 2402 (referred to as the ucp gene-activating region), which has an enhancer activity but cannot confer RA response to a promoter. This response was obtained with a larger DNA fragment (bp 2489 to 2398) constituting a complex RA response domain.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. CANNON and J. NEDERGAARD Brown Adipose Tissue: Function and Physiological Significance Physiol Rev, January 1, 2004; 84(1): 277 - 359. [Abstract] [Full Text] [PDF]

				J. S. Rim and L. P. Kozak Regulatory Motifs for CREB-binding Protein and Nfe2l2 Transcription Factors in the Upstream Enhancer of the Mitochondrial Uncoupling Protein 1 Gene J. Biol. Chem., September 6, 2002; 277(37): 34589 - 34600. [Abstract] [Full Text] [PDF]

				A. M. Lennon, M. Ramauge, A. Dessouroux, and M. Pierre MAP Kinase Cascades Are Activated in Astrocytes and Preadipocytes by 15-Deoxy-Delta 12-14-prostaglandin J2 and the Thiazolidinedione Ciglitazone through Peroxisome Proliferator Activator Receptor gamma -independent Mechanisms Involving Reactive Oxygenated Species J. Biol. Chem., August 9, 2002; 277(33): 29681 - 29685. [Abstract] [Full Text] [PDF]

				H. Oberkofler, H. Esterbauer, V. Linnemayr, A. D. Strosberg, F. Krempler, and W. Patsch Peroxisome Proliferator-activated Receptor (PPAR) gamma Coactivator-1 Recruitment Regulates PPAR Subtype Specificity J. Biol. Chem., May 3, 2002; 277(19): 16750 - 16757. [Abstract] [Full Text] [PDF]

				S. Collins, W. Cao, K. W. Daniel, T. M. Dixon, A. V. Medvedev, H. Onuma, and R. Surwit Adrenoceptors, Uncoupling Proteins, and Energy Expenditure Experimental Biology and Medicine, December 1, 2001; 226(11): 982 - 990. [Abstract] [Full Text] [PDF]

				S. Viengchareun, P. Penfornis, M.-C. Zennaro, and M. Lombes Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E640 - E649. [Abstract] [Full Text] [PDF]

				P. Yubero, M. Barberá, R. Alvarez, O. Viñas, T. Mampel, R. Iglesias, F. Villarroya, and M. Giralt 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., July 1, 1998; 12(7): 1023 - 1037. [Abstract] [Full Text]

				M. del Mar Gonzalez-Barroso, C. Pecqueur, C. Gelly, D. Sanchis, M.-C. Alves-Guerra, F. Bouillaud, D. Ricquier, and A.-M. Cassard-Doulcier Transcriptional Activation of the Human ucp1 Gene in a Rodent Cell Line. SYNERGISM OF RETINOIDS, ISOPROTERENOL, AND THIAZOLIDINEDIONE IS MEDIATED BY A MULTIPARTITE RESPONSE ELEMENT J. Biol. Chem., October 6, 2000; 275(41): 31722 - 31732. [Abstract] [Full Text] [PDF]