RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes.
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.
Kiskinis
Evangelos
E
Molecular Endocrinology Laboratory, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK.
Hallberg
Magnus
M
Christian
Mark
M
Olofsson
Martina
M
Dilworth
Stephen M
SM
White
Roger
R
Parker
Malcolm G
MG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000502:physiology*; D052438:Adipocytes, White / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D007473:Ion Channels / Q000096:biosynthesis*; D051379:Mice; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D000071256:Uncoupling Protein 1
D048868:Adaptor Proteins, Signal Transducing; D006657:Histones; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D004247:DNA