The DOI matches its Crossref record; 74 of the 78 references it cites were found in a registry or an index.
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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“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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Citations
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Items 401–466 of 466
New Insights in Adipose Tissue Biology: From Obesity to Therapeutic Prospects
Colitti, M. (2012) · Endocrinology & Metabolic Syndrome · doi:10.4172/2161-1017.1000e103 · Cited by 1
“These cells can be converted to brown adipocyte–like cells and appear in white fat depots [9].”
BackgroundEVI1 Mediated Stimulation of 3T3-L1 Preadipocyte Differentiation Is CtBP Dependent
Ireland, M. J., Alhasan, M. A., Craft, J. A., Graham, A., & Bartholomew, C. (2017) · Yangtze Medicine · doi:10.4236/ym.2017.13014 · Cited by 1
“Furthermore, the EVI1 related protein PRDM16 also binds CtBP proteins to repress white fat specific genes and are displaced to promote brown adipose tissue development [35].”
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Paniagua, J. A., & Vidal‐Puig, A. (2023) · Springer eBooks · doi:10.1007/978-3-031-25519-9_14 · Cited by 1
Immunoprecipitation with an Anti-Epitope Tag Affinity Gel to Study Protein-Protein Interactions
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Adipose Tissue Development, Structure and Function
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“…homologous (PR) domain and several zinc fingers, has been shown t turn on the expression of brown fat-selective genes and turn off the expression of white fat-enriched genes, and therefore acts as an critical regulator during adipose development (Seale et al., 2007; Kajimura et al., 2008).”
BackgroundNew Therapeutic Targets for Obesity Treatment in Basic Medical Science
Lee, S. (2012) · The Korean Journal of Obesity · doi:10.7570/kjo.2012.21.3.125 · Cited by 1
Song, Z. (2017) · TSpace (University of Toronto) · Cited by 1
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Halpérin, D. (2012) · eScholarship (California Digital Library)
Rizki, G. (2011) · eCommons (Cornell University)
Research Highlight The Engineering of Brown Fat
Christian, M., & Parker, M. G. (2015)
BROWN ADIPOSE TISSUE IN ADULT HUMAN
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Amplification of PRDM16, BMP7, PPARα, COX II and PGC-1α Genes Tupaia belangeri
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Change in Ca2+-responses of cultivated brown adipocytes at adrenergic activation
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“The authors identified the mechanism and used it to show that PRDM16, the main regulator of the formation and functioning of brown adipocytes, could simultaneously induce the expression of BAT genes and suppress the expression of genes of white adipose tissue (Kajimura et al., 2008).”
MethodBrown Adipose Tissue Differentiation and Control Mechanism
张, 麟. (2011) · Bioprocess · doi:10.12677/bp.2011.12004
Brown Adipose Tissue as a Therapeutic Target
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Role of Energy Metabolism in the Thermogenic Gene Program
Nam, M. (2017) · eScholarship@UMassChan · doi:10.13028/m2np4f
“This is achieved by forming a transcriptional repressor complex with CtBP1 and CtBP2 (39).”
BackgroundINDUCTION OF BROWN ADIPOSE TISSUE: A REVIEW
Romauld, S. I., Akilashree, S., & Devi, P. B. (2018) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2018.v11i5.22646
Role of Exercise on Beige Cell
Lee, H. J. (2018) · 한국체육학회지 · doi:10.23949/kjpe.2018.03.57.2.37
Obesity in the Pathophysiology of Diabetes
Paniagua, J. A., & Vidal‐Puig, A. (2019) · Springer eBooks · doi:10.1007/978-3-030-11815-0_13
Regulation of thermogenesis in Brown and Beige Adipose Tissues
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“PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16) is a critical regulator controlling brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat [13].”
BackgroundEvidence of Browning Phenomenon and Its Physiological Relevance in Non-Adipose TissuesPreprint
Ho, D. H.-H., Moola, M. R., Lung, H. L., Yau, K.-H., Chan, H. Y.-S., Yuen, S.-N., Yue, P. Y., & Wong, R. H.-F. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3363905
PRDM proteins control Wnt/β-catenin activity to regulate craniofacial chondrocyte differentiationPreprint
Shull, L. C., Kim, H. M., Lencer, E. S., Goyama, S., Kurokawa, M., Costello, J. C., Jones, K. L., & Artinger, K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.21.445211
“PRDM3 and PRDM16 are important in a variety of developmental processes in mouse and zebrafish, acting as both repressors and activators of specific GRNs depending on cellular context [54, 60-71].”
BackgroundMiyata, T., & Ichimura, A. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718167526.793488225
Borrell, V. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733272146.793566102
Faculty Opinions recommendation of Adaptive thermogenesis in adipocytes: is beige the new brown?
Symonds, M. E. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717979561.793471365
XBP1: An Adaptor in the Pathogenesis of AtherosclerosisPreprint
Wang, T., Zhou, J., Zhang, X., Wu, Y., Jin, K., Wang, Y., Xu, R., Yang, G., Li, W., & Jiao, L. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4152835
Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage
Vasilyev, S. А., Vasilyeva, O. Y., Oppong-Peprah, B., Demeneva, V. V., Zuev, A. S., Sazhenova, E. A., Tv, N., & Tolmacheva, E. N. (2023) · RUDN Journal of Medicine · doi:10.22363/2313-0245-2023-27-4-515-531
Szeder, B. (2023) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2022.152
The Functions of PRDM3 in Different Cell Behaviors
Li, X. (2024) · Journal of Student Research · doi:10.47611/jsr.v13i1.1835
Castelli, J. Z., Raposo, H. F., Navarro, C. D. C., Lázaro, C. M., Sartori, M. R., Costa, A. P. D., Nogueira, P. A. S., Velloso, L. A., Vercesi, A. E., & Oliveira, H. C. F. (2025) · The FASEB Journal · doi:10.1096/fj.202402843rr · Cited by 1
“34,35 We have previously reported that under chow diet and housing temperature at 22°C, CETP expression increases white and brown adipose lipolysis, BAT oxygen consumption, and body metabolic rate, resulting in reduced adipose tissue mass as compared to NTg mice.”
PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferationPreprint
He, L., Wen, J., & Dai, Q. (2025) · eLife · doi:10.7554/elife.104076.1
E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression
Rivera, F. V., Furino, V. D. O., Leher, C. E. P., Zanesco, A. M., Angelim, M. K. S. C., Gan, F. C., Santoro, A. L., Regina-Ferreira, L., Santos, G. L., Gonçalves, T. T., et al. (2026) · EMBO Reports · doi:10.1038/s44319-026-00826-0
“Previous studies revealed that Prdm16 is involved in the transcriptional repression programs in adipocytes (Hasegawa et al, 2018; Kajimura et al, 2008; Kissig et al, 2017).”
Self-citationPRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferationPreprint
He, L., Wen, J., & Dai, Q. (2025) · eLife · doi:10.7554/elife.104076.2
Rajakumari, S., & Divakaran, S. J. (2025) · Journal of Lipid Research · doi:10.1016/j.jlr.2025.100888
“In particular, EBF2 dictates PPAR γ , the master regulator of adipogenesis, to bind onto BAT-specific gene loci and acts upstream of PRDM16, a BAT-specific transcription factor (28, 29).”
Transcriptional Control of Gene Expression in Different Adipose Tissue Depots
Farmer, S. R. (2010) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-642-13517-0_9
“Recent studies by Spiegelman and colleagues showed that induction of the brown phenotype by PRDM16 during brown adipogenesis also involved repression of select genes, including resistin, through mechanisms that required association of PRDM16 with CtBPs ( Kajimura et al., 2008 ).”
BackgroundSalmón‐Gómez, L., Gómez‐Ambrosi, J., Frühbeck, G., & Catalán, V. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00346-0
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“As described in adipose, 17,82 neuronal, 83,84 and cardiac tissue, 23 we found that Prdm16 exerts its endothelial function via binding to other TFs. Specifically, Prdm16 enhanced canonical Notch activity in 2 separate and compatible ways, including its direct binding to NICD, congruent with our…”
Lecoutre, S. (2017) · theses.fr (ABES) · doi:10.70675/65a35937ze6d1z436ezb142z7812e3f38007
Étude du rôle de PRDM16 dans l'activation des cellules hépatiques stellaires
Mesdom, P. (2017) · theses.fr (ABES) · doi:10.70675/12e4a8f0z6895z41dfz8de6zbd1602bea2c5
Rôle de la mPGES-1 dans le développement de l'inflammation chronique de bas seuil et de l'obésité
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Métabolisme redox et plasticité tissulaire des tissus adipeux
Jeanson, Y. (2015) · theses.fr (ABES) · doi:10.70675/0a5580f9z0185z4ab1zba28zb59c62a27680
Zhang, Y., Zheng, Y., Chen, B., Li, X., Zhang, T., Xu, L., Ma, J., Ma, X., & Li, Y. (2026) · Science China Life Sciences · doi:10.1007/s11427-025-3228-2
“Notably, although PRDM16 and HSF1 both generally functioned as transcriptional activators, they were shown to recruit repressive factors for the transcriptional inhibition of certain genes (Kajimura et al., 2008; Khaleque et al., 2008).”
PRDM3 and PRDM16 define cranial neural crest cell states in zebrafish development
Shull, L. C., Meyer‐Nava, S., Saxton, B., Denipah-Cook, Q., Raha, F., Roffers‐Agarwal, J., Flores, J., Lencer, E. S., Ramachandran, S., & Artinger, K. (2026) · Differentiation · doi:10.1016/j.diff.2026.100990
Abdi, A. (2025) · Physiology and Pharmacology · doi:10.66224/phypha.29.4.398
“…gene programs (i.e., myogenic genes or genes associated with white fat) and activates a brown fat-specific gene program, which includes UCP-1, Per - oxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α), along with numerous mi - tochondrial genes (Kajimura et al., 2008).”
Dai, Q., & Shu, R. (2026) · Pharmaceuticals · doi:10.3390/ph19091469
“Its PR domain catalyzes histone H3 lysine methylation [30,31], thereby modulating chromatin accessibility, together with a PLDLS motif that recruits the corepressors CtBP1/2 [32] and two zinc finger clusters that mediate multi-protein assembly [33] (Figure 1).”
Choi, Y., Lee, E. S., Park, J. W., Baik, J. Y., Chung, H. K., & Kang, J. H. (2026) · Scientific Reports · doi:10.21203/rs.3.rs-10889202/v1
Deng, X., Shen, Y., Sun, Y. H., Lu, L., & Sun, C. (2026) · MedComm · doi:10.1002/mco2.70976
“…such as PPAR γ and C/EBP β to recruit activating complexes to target genes, strongly activating BAT-selective gene programs [ 60 ], on the other hand, it actively represses white adipocyte-specific genes by forming inhibitory complexes with CtBP1/2, thereby refining lineage commitment [ 61 ].”
ETS-2 deficiency impairs brown adipose tissue function through Prdm16 repression
Chen, H., Zhai, X., Zhang, Y., Chen, K., Fu, L., Hu, D., Zheng, Z., Guan, S., Qu, X., & Ye, M. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156788
Role of Tyk2 in the Development of Beige Cells
Umali, S. (2011) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/vbwv-1t33
Metadata
- 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 (medical) › 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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