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Molecular and Cellular Biology, November 2005, p. 9383-9391, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9383-9391.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

RIP140-Targeted Repression of Gene Expression in Adipocytes

Mark Christian,1 Evangelos Kiskinis,1 Darja Debevec,1 Göran Leonardsson,2 Roger White,1 and Malcolm G. Parker1*

Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom,1 Arexis AB, Arvid Wallgrens Backe, 20 SE-413 46 Göteborg, Sweden2

Received 4 March 2005/ Returned for modification 8 April 2005/ Accepted 5 August 2005

Ligand-dependent repression of nuclear receptor activity forms a novel mechanism for regulating gene expression. To investigate the intrinsic role of the corepressor RIP140, we have monitored gene expression profiles in cells that express or lack the RIP140 gene and that can be induced to undergo adipogenesis in vitro. In contrast to normal white adipose tissue and in vitro-differentiated wild-type adipocytes, RIP140-null cells show elevated energy expenditure and express high levels of the uncoupling protein 1 gene (Ucp1), carnitine palmitoyltransferase 1b, and the cell-death-inducing DFF45-like effector A. Conversely, all these changes are abrogated by the reexpression of RIP140. Analysis of the Ucp1 promoter showed RIP140 recruitment to a key enhancer element, demonstrating a direct role in repressing gene expression. Therefore, reduction in the levels of RIP140 or prevention of its recruitment to nuclear receptors may provide novel mechanisms for the control of energy expenditure in adipose cells.

* Corresponding author. Mailing address: Imperial College London, IRDB, Du Cane Road, London W12 0NN, United Kingdom. Phone: 44(0)2075942177. Fax: 44(0)2075942184. E-mail: m.parker{at}imperial.ac.uk.

Molecular and Cellular Biology, November 2005, p. 9383-9391, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9383-9391.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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