Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
Open accessAbstract
Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16 is a zinc-finger protein that controls brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat cells. To determine the mechanisms regulating this switching of gene programs, we purified native PRDM16 protein complexes from fat cells. We show here that the PRDM16 transcriptional holocompex contains C-terminal-binding protein-1 (CtBP-1) and CtBP-2, and this direct interaction selectively mediates the repression of white fat genes. This repression occurs through recruiting a PRDM16/CtBP complex onto the promoters of white fat-specific genes such as resistin, and is abolished in the genetic absence of CtBP-1 and CtBP-2. In turn, recruitment of PPAR-γ-coactivator-1α (PGC-1α) and PGC-1β to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1α itself. These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs.
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The effect of PRDM16 depends on interaction with PGC-1α/β, PPARγ and C/EBPβ, while binding to CtBP-1 and CtBP-2 suppresses expression of white fat-selective genes.
“This effect depends on the interaction of PRDM16 with PGC-1α/β, PPARγ and C/EBPβ, while binding of PRDM16 to CtBP-1 and CtBP-2 suppresses expression of white fat-selective genes 171,172.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [171]
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Self-citation
- Authors
- Kajimura, S., Seale, P., Tomaru, T., Erdjument-Bromage, H., Cooper, M. P., Ruas, J. L., Chin, S., Tempst, P., Lazar, M. A., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- University of Pennsylvania (US)
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-05-15
- Volume
- 22
- Issue
- 10
- Pages
- 1397-1409
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2377193
- OpenAlex
- W2163468424
- Cited by
- 468
- References
- 78
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 13 · 2023: 16 · 2022: 18 · 2021: 21 · 2020: 25 · 2019: 22 · 2018: 27 · 2017: 35 · 2016: 30 · 2015: 46 · 2014: 33 · 2013: 28 · 2012: 32
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wenner-Gren Foundation
- University of Pittsburgh
- National Institutes of Health (CA08748)
- National Cancer Institute (P30-CA-08748, CA08748, P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK-31405, P01DK049210, DK 49210, R37DK031405)
- 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
- PRDM16, brown adipose tissue, white adipose tissue, transcriptional repression, PGC-1α, PGC-1β, resistin, transcriptional complex, gene expression regulation, obesity
- MeSH terms
- Alcohol Oxidoreductases, Animals, Adipose Tissue, Brown, Cell Differentiation, Chlorocebus aethiops, DNA-Binding Proteins, Gene Expression Regulation, Genes, Regulator, Models, Biological, Phosphoproteins, Protein Binding, Transcription Factors, Transcription, Genetic, 3T3 Cells, COS Cells, 3T3-L1 Cells, Multiprotein Complexes, Mice, Adipose Tissue, White, Co-Repressor Proteins
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