RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes

Evangelos Kiskinis, Magnus Hallberg, Mark Christian, Martina Olofsson, Stephen M. Dilworth, Roger White, Malcolm G. Parker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4831-4840
Number of pages10
JournalEMBO Journal
Volume26
Issue number23
DOIs
StatePublished - Nov 28 2007

Keywords

  • Adipocytes
  • DNA methylation
  • Nuclear receptors
  • RIP140
  • Ucp1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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