Transcriptional regulation of the uncoupling protein-1 gene
Abstract
Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated, thermogenically competent status of brown and beige/brite adipocytes, as well as of the responsiveness of brown and beige/brite adipocytes to adaptive regulation of thermogenic activity. The 5' non-coding region of the UCP1 gene contains regulatory elements that confer tissue specificity, differentiation dependence, and neuro-hormonal regulation to UCP1 gene transcription. Two main regions-a distal enhancer and a proximal promoter region-mediate transcriptional regulation through interactions with a plethora of transcription factors, including nuclear hormone receptors and cAMP-responsive transcription factors. Co-regulators, such as PGC-1α, play a pivotal role in the concerted regulation of UCP1 gene transcription. Multiple interactions of transcription factors and co-regulators at the promoter region of the UCP1 gene result in local chromatin remodeling, leading to activation and increased accessibility of RNA polymerase II and subsequent gene transcription. Moreover, a commonly occurring A-to-G polymorphism in close proximity to the UCP1 gene enhancer influences the extent of UCP1 gene transcription. Notably, it has been reported that specific aspects of obesity and associated metabolic diseases are associated with human population variability at this site. On another front, the unique properties of the UCP1 promoter region have been exploited to develop brown adipose tissue-specific gene delivery tools for experimental purposes.
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T3 regulates mitochondrial uncoupling by sympathetic stimulation, by increasing acylcarnitine production, and by directly stimulating transcription of the Ucp1 gene.
“T3 regulates mitochondrial uncoupling by different mechanisms: (1) by sympathetic stimulation [61], (2) by increasing acylcarnitine production [61], thereby activating mitochondrial respiration/uncoupling, and (3) by directly stimulating the transcription of the Ucp1 gene [37].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [37]
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- Authors
- Villarroya, F., Peyrou, M., & Giralt, M.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Villarroya, Francesc
- Venue
- Biochimie
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 134
- Pages
- 86-92
- ISSN
- 0037-9042 (ISSN-L)
- 0300-9084
- OpenAlex
- W2529255361
- Cited by
- 108
- References
- 99
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 16 · 2020: 14 · 2019: 15 · 2018: 6 · 2017: 4
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimie (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Ciencia e Innovación (PI14/00063)
- European Regional Development Fund
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- UCP1, brown adipocytes, thermogenesis, 5' untranslated region, enhancers, promoter, nuclear receptors, PGC-1α, coregulators, chromatin remodeling, obesity, transcriptional regulation
- MeSH terms
- Adipose Tissue, Beige, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Gene Expression Regulation, Humans, Obesity, Promoter Regions, Genetic, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Receptors, Cytoplasmic and Nuclear, Thermogenesis, Mice, Adipose Tissue, White
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