Article
- The EMBO Journal (2007) 26, 4831 - 4840
- doi:10.1038/sj.emboj.7601908
Published online: 1 November 2007
Subject Categories:
RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes
Evangelos Kiskinis1, Magnus Hallberg1, Mark Christian1, Martina Olofsson2, Stephen M Dilworth2, Roger White1 and Malcolm G Parker1
- Molecular Endocrinology Laboratory, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK
- Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, London, UK
Correspondence to:
Malcolm G Parker, Molecular Endocrinology Laboratory, Institute of Reproductive and Development Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. Tel.: +44 20 7594 2177; Fax: +44 20 7594 2184; E-mail: m.parker@imperial.ac.uk
Received 26 April 2007; Accepted 9 October 2007
Abstract
Nuclear receptors control the function of cells by regulating transcription from specific gene networks. The establishment and maintenance of epigenetic gene marks is fundamental to the regulation of gene transcription and the control of cell function. RIP140 is a corepressor for nuclear receptors that suppresses transcription from a broad programme of metabolic genes and thereby controls energy homoeostasis in vivo. Here we show by analysis of Ucp1, a gene which is typically expressed in brown but not white adipocytes, that RIP140 is essential for both DNA and histone methylation to maintain gene repression. RIP140 expression promotes the assembly of DNA and histone methyltransferases (HMTs) on the Ucp1 enhancer and leads to methylation of specific CpG residues and histones as judged by bisulphite genomic sequencing and chromatin immunoprecipitation assays. Our results suggest that RIP140 serves as a scaffold for both DNA and HMT activities to inhibit gene transcription by two key epigenetic repression systems.
Keywords:
- adipocytes,
- DNA methylation,
- nuclear receptors,
- RIP140,
- Ucp1
