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RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes
Open accessAbstract
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.
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“Nuclear co-repressor RIP140 directs histone and DNA methylation to silence UCP1 expression and suppress mitochondrial biogenesis in white adipocytes 169,170.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [169]
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Metadata
- Authors
- Kiskinis, E., Hallberg, M., Christian, M., Olofsson, M., Dilworth, S. M., White, R., & Parker, M. G.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Parker, Malcolm G
- Venue
- The EMBO Journal
- Published
- 2007-11-01
- Volume
- 26
- Issue
- 23
- Pages
- 4831-4840
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2099470
- OpenAlex
- W2082416078
- Cited by
- 111
- References
- 57
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 4 · 2012: 8
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (504327, 079200/Z/06/Z)
- Biotechnology and Biological Sciences Research Council (BB/C504327/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- RIP140, UCP1, white adipocytes, histone methylation, DNA methylation, epigenetic silencing, nuclear receptor corepressor, histone methyltransferase, DNA methyltransferases, CpG methylation, enhancers, transcriptional repression, energy homeostasis
- MeSH terms
- Uncoupling Protein 1, Nuclear Receptor Interacting Protein 1, Animals, Cell Differentiation, Cell Nucleus, DNA, Fibroblasts, Gene Expression Regulation, Histones, Ion Channels, Nuclear Proteins, CpG Islands, DNA Methylation, Mitochondrial Proteins, Epigenesis, Genetic, Chromatin Immunoprecipitation, Adaptor Proteins, Signal Transducing, Mice, Adipocytes, White
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