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J. Biol. Chem., Vol. 281, Issue 43, 32140-32147, October 27, 2006

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RIP140 Expression Is Stimulated by Estrogen-related Receptor during Adipogenesis^*

From the Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, London W12 0NN, United Kingdom

RIP140 is a corepressor for nuclear receptors that regulates energy expenditure in adipose tissue by suppressing the expression of clusters of metabolic genes involved in glucose and lipid metabolism. The gene encoding RIP140/Nrip1 contains only one coding exon but has multiple promoters and 5' non-coding exons that are subject to alternative splicing. In adipocytes we have defined a promoter, referred to as P2, that is preferentially utilized and activated during adipogenesis. Expression studies and chromatin immunoprecipitation experiments indicate that estrogen-related receptor (ERR), the level of which increases during adipogenesis in parallel with RIP140, stimulates transcription from the P2 promoter. Further analysis indicates that ERR is capable of activating RIP140 gene transcription by two mechanisms, directly by binding to an estrogen receptor element/ERR element at –650/–633 and indirectly through Sp1 binding sites in the proximal promoter. Thus, the up-regulation of RIP140 by ERR during adipogenesis may provide an inhibitory feedback mechanism to control the expression of many nuclear receptor target genes.

Received for publication, May 18, 2006 , and in revised form, June 30, 2006.

^* This work was supported by Ph.D. Studentship Grant 02/B1/S/08214 (to D. N.) and Wellcome Trust Grant 061930 (to M. C. and J. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ To whom correspondence should be addressed: Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, London, Du Cane Rd., London W12 0NN, UK. Tel.: 44-20-7594-2177; Fax: 44-20-7594-2184; E-mail: m.parker{at}imperial.ac.uk.

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