Affinage

PRDM16

Histone-lysine N-methyltransferase PRDM16 · UniProt Q9HAZ2

Length
1276 aa
Mass
140.3 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRDM16 is a zinc-finger transcriptional co-regulator that governs cell-fate decisions and tissue identity across adipose, muscle, neural, hematopoietic, intestinal, and cardiac lineages by nucleating context-dependent chromatin complexes and by exerting intrinsic histone methyltransferase activity (PMID:18719582, PMID:22939622, PMID:27151440). Its best-defined role is establishing brown/beige adipocyte identity: PRDM16 binds PGC-1α/β and PPARγ to activate thermogenic genes, acts as a bidirectional switch between brown fat and skeletal myoblast fates, and is required cell-autonomously to maintain brown/beige character and suppress white-fat and visceral-like programs (PMID:17618855, PMID:18719582, PMID:21123942, PMID:24439384). The directionality of this output is set by the cofactors it recruits—CtBP-1/2 and TLE3 enforce repression of brown-selective genes or disrupt the PRDM16–PPARγ interaction, while C/EBP-β(LAP), MED1/Mediator, EHMT1, and GTF2IRD1 promote the thermogenic and anti-fibrotic programs (PMID:18483224, PMID:19641492, PMID:23473036, PMID:25644605, PMID:29320702). PRDM16 carries two enzymatic activities: a Prdm3-redundant H3K9me1 methyltransferase activity that seeds heterochromatin, and a PR-domain H3K4 methyltransferase activity that activates target genes such as Gfi1b to suppress MLL-fusion leukemogenesis (PMID:22939622, PMID:27151440). Beyond catalysis it engages chromatin machinery directly, binding RBBP4/NuRD through its N-terminal PR-domain region within the histone H3-binding groove and localizing to the nuclear lamina to tether and silence alternative-fate genes (PMID:30462309, PMID:34078594). PRDM16 abundance is the principal control point for its activity and is set by competing post-translational modifications: CUL2-APPBP2 polyubiquitination drives degradation, CBX4 sumoylation at K917 and EHMT1 binding stabilize the protein, and acetylation at K915 by BCKA-derived acetyl-CoA disrupts the PRDM16–PPARγ interaction (PMID:24196706, PMID:29539416, PMID:35978186, PMID:35075301). In other tissues PRDM16 sustains hematopoietic and neural stem-cell maintenance and quiescence, directs intestinal crypt fatty-acid oxidation, specifies compact-versus-trabecular myocardium with Tbx5/Hand1, and defines a tolerogenic dendritic-cell subset that supports peripheral regulatory T-cell differentiation (PMID:20835244, PMID:33268499, PMID:31564549, PMID:34915728, PMID:40228524). A loss-of-function PRDM16 Q187X variant impairs cardiomyocyte proliferation and dysregulates TGF-β transcripts, linking the gene to human cardiomyopathy (PMID:38113297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2003 Medium

    Established that PRDM16 (MEL1) is a sequence-specific DNA-binding transcription factor whose PR-domain-lacking short isoform has distinct activity, raising the question of isoform-specific function.

    Evidence DNA-binding consensus (CASTing), reporter and GAL4-fusion assays, and G-CSF differentiation in myeloid cells

    PMID:12816872

    Open questions at the time
    • Endogenous direct target genes not defined
    • Mechanism distinguishing MEL1 vs MEL1S in vivo unresolved
  2. 2007 High

    Defined PRDM16 as a brown-fat determinant acting through direct binding to PGC-1 coactivators, answering how a single factor could drive a thermogenic gene program.

    Evidence Co-IP, shRNA, and ectopic expression in white fat progenitors with brown-fat gene readout

    PMID:17618855

    Open questions at the time
    • Did not address muscle-vs-fat fate choice
    • Did not resolve repressive vs activating complex composition
  3. 2008 High

    Showed PRDM16 is a bidirectional brown-fat/myoblast fate switch acting via PPARγ, and that a CtBP-containing complex enforces repression of white-fat genes displaced by PGC-1 for activation, establishing the cofactor-swap logic.

    Evidence Myf5-Cre lineage tracing, gain/loss of function, reciprocal Co-IP, native complex purification and ChIP with CtBP knockout

    PMID:18483224 PMID:18719582

    Open questions at the time
    • Genome-wide partition of activated vs repressed targets not mapped
    • Cue that triggers CtBP-to-PGC-1 exchange not identified
  4. 2009 High

    Demonstrated PRDM16 with C/EBP-β is sufficient to reprogram fibroblasts to functional brown fat, defining a minimal initiating complex for the thermogenic program.

    Evidence Co-IP/MS complex identification, fibroblast co-expression, transplantation with PET-FDG imaging

    PMID:19641492

    Open questions at the time
    • Order of complex assembly during reprogramming unclear
    • Role of endogenous loci accessibility not addressed
  5. 2010 High

    Extended PRDM16 to subcutaneous beige adipocytes and to stem-cell maintenance, showing it is cell-autonomously required for thermogenesis and for HSC/NSC maintenance via ROS control and Hgf regulation.

    Evidence shRNA and respiration assays in adipocytes; germline KO with ChIP, ROS measurement, and HGF/NAC rescue in stem cells

    PMID:20835244 PMID:21123942

    Open questions at the time
    • Direct adipocyte targets in subcutaneous fat not enumerated
    • Mechanism linking PRDM16 to ROS homeostasis incomplete
  6. 2012 High

    Identified PRDM16's intrinsic H3K9me1 methyltransferase activity (redundant with Prdm3) and showed PPARγ agonists act by stabilizing PRDM16 protein, splitting its function into a catalytic chromatin role and a post-translationally controlled abundance.

    Evidence In vitro methyltransferase assay, MEF double-knockdown with FISH/EM; cycloheximide-chase half-life and in vivo agonist synergy

    PMID:22405074 PMID:22939622

    Open questions at the time
    • Coupling of cytoplasmic H3K9me1 activity to nuclear gene regulation unclear
    • Identity of the agonist-controlled degradation machinery not yet defined
  7. 2013 High

    Resolved how PRDM16 selects brown vs white output by defining EHMT1 as an essential activating/stabilizing component and TLE3 as a white-selective cofactor that disrupts the PRDM16–PPARγ interaction.

    Evidence Co-IP, H3K9 methylation analysis, adipocyte EHMT1 conditional KO; Co-IP disruption assay and reciprocal TLE3 transgenic/KO mice

    PMID:23473036 PMID:24196706

    Open questions at the time
    • Competition kinetics between EHMT1, TLE3 and PPARγ not quantified
    • Signals controlling cofactor selection in vivo unknown
  8. 2014 High

    Distinguished developmental dispensability from maintenance requirement: PRDM16 (with Prdm3) is needed to suppress white-fat genes in BAT via Ehmt1 recruitment and to preserve beneficial subcutaneous fat identity.

    Evidence Brown-lineage and adipocyte-specific conditional KOs, Ehmt1 recruitment assay, double KO, and fat transplantation

    PMID:24439384 PMID:24703692

    Open questions at the time
    • Aging-related trigger of identity loss not mechanistically resolved
    • Extent of Prdm3 compensation across depots unclear
  9. 2015 High

    Established a direct enhancer-activation mechanism whereby PRDM16 zinc fingers bind MED1/Mediator to potentiate TR-driven Ucp1 transcription.

    Evidence In vitro binding with domain mutagenesis, ChIP to Ucp1 enhancer, reconstituted in vitro transcription, cell-based MED1-dependence

    PMID:25644605

    Open questions at the time
    • Generality of MED1 recruitment across PRDM16 targets not tested
    • Interplay with histone-modifying cofactors at the same enhancer unresolved
  10. 2016 High

    Demonstrated a second catalytic activity—PR-domain H3K4 methyltransferase—that activates Gfi1b to suppress MLL-fusion leukemogenesis, expanding PRDM16 into a tumor-suppressive chromatin role.

    Evidence In vitro HMT assay, PR-domain mutagenesis, in vivo leukemogenesis models, ChIP and Gfi1b knockdown

    PMID:27151440

    Open questions at the time
    • Substrate specificity (H3K4 vs H3K9) context-dependence unresolved
    • Whether the same activity operates in adipose not addressed
  11. 2017 High

    Broadened PRDM16 into immune and stress regulation, showing it represses type I interferon-stimulated genes by blocking IRF1 and acts in neural stem cells to drive ependymal Foxj1 expression.

    Evidence ChIP and conditional KO with IFN activation in adipose; Nestin-Cre conditional deletion with ependymal/NSC phenotyping

    PMID:28408438 PMID:28698301

    Open questions at the time
    • Direct molecular contact with IRF1 not structurally defined
    • Foxj1 regulation mechanism (direct vs indirect) not fully resolved
  12. 2018 High

    Defined UCP1-independent and structural facets: a cold-inducible GTF2IRD1-containing complex represses pro-fibrosis genes, PRDM16 binds RBBP4/NuRD via its PR-domain region within the H3 groove, and its methyltransferase domain shapes cortical neuron positioning.

    Evidence Complex purification/ChIP with GTF2IRD1 genetics; ITC and crystallography of PRDM16–RBBP4; radial-glia conditional KO with ChIP-seq and domain-mutant rescue

    PMID:29320702 PMID:29779941 PMID:30462309

    Open questions at the time
    • Functional consequence of NuRD recruitment on specific loci not mapped
    • How PR-domain binding partitions between RBBP4 and catalysis unclear
  13. 2019 High

    Linked PRDM16 to metabolite signaling and tissue-specific metabolism: PRDM16+ adipocytes secrete BHB to block fibrogenesis and enable beige adipogenesis, and PRDM16 controls fatty-acid oxidation in intestinal crypt progenitors.

    Evidence Conditional KO with metabolite profiling, BDH1 KO and dietary BHB rescue; inducible intestinal KO with ChIP-seq/RNA-seq and acetate rescue

    PMID:31155495 PMID:31564549

    Open questions at the time
    • Transcriptional mechanism coupling PRDM16 to BHB output not detailed
    • Whether intestinal FAO control uses the same cofactor complexes unknown
  14. 2020 Medium

    Established PRDM16 in HSC quiescence and cardiac homeostasis, regulating Cdkn1a/Egr1 to enforce LT-HSC dormancy and cooperating with Ehmt to restrain pro-hypertrophic Myc and fetal-gene reactivation in heart.

    Evidence Inducible HSC KO with cell-cycle analysis and ChIP; cardiac-specific KO with fibrosis, mitochondrial, and Ehmt-Myc axis analysis

    PMID:33086060 PMID:33268499

    Open questions at the time
    • Single-lab studies without cross-lab replication
    • Direct vs indirect regulation of Myc not fully established
  15. 2021 High

    Defined nuclear-lamina-mediated repression and cardiac chamber identity: PRDM16 with G9a/GLP tethers myogenic genes at the nuclear periphery in FAPs, and with Tbx5/Hand1 specifies compact vs trabecular myocardium.

    Evidence Nuclear fractionation, LAD analysis, G9a/GLP disruption with FAP fate readout; cardiomyocyte KO with RNA-seq, ChIP-seq, scRNA-seq, spatial transcriptomics

    PMID:34078594 PMID:34915728

    Open questions at the time
    • How PRDM16 is recruited to the lamina mechanistically unknown
    • Direct vs cooperative DNA binding with Tbx5/Hand1 not dissected
  16. 2022 High

    Identified the dominant abundance-control axis: CUL2-APPBP2 polyubiquitinates and degrades PRDM16 (elevated with aging), while BCKA-derived acetyl-CoA acetylates K915 to disrupt the PRDM16–PPARγ interaction, defining druggable nodes for thermogenesis.

    Evidence E3-ligase identification with ubiquitination/half-life assays and adipocyte KO; MS-mapped K915 acetylation with mutagenesis, Co-IP disruption, and Bcat2 KO mice

    PMID:35075301 PMID:35978186

    Open questions at the time
    • Interplay among K915 acetylation, K917 sumoylation, and ubiquitination not integrated
    • Upstream signals regulating CUL2-APPBP2 abundance unclear
  17. 2023 Medium

    Connected PRDM16 to vascular and human cardiac disease: it represses ADAM12 in VSMCs to limit aneurysm-associated ECM remodeling, and a human Q187X loss-of-function variant impairs cardiomyocyte proliferation with TGFB3 dysregulation.

    Evidence ChIP and VSMC-specific KO with elastase AAA model and Adam12 rescue; ChIP/reporter, iPSC-CMs from a Q187X proband, and CRISPR knock-in mouse

    PMID:37079380 PMID:38113297

    Open questions at the time
    • Single-lab disease models
    • Mechanism of TGF-β transcript dysregulation beyond TGFB3 incomplete
  18. 2024 Medium

    Expanded PRDM16 into renal redox protection and vascular circadian/blood-pressure control, binding TRPA1/NRF2 promoters to suppress ferroptosis and regulating Adra1d and clock genes in VSMCs.

    Evidence ChIP with proximal-tubule KO/knock-in in sepsis models; VSMC-specific KO with telemetry, contraction assays, and clock-gene analysis

    PMID:39549609 PMID:39625782

    Open questions at the time
    • Direct vs indirect activation of NRF2/TRPA1 not fully resolved
    • Single-lab findings awaiting replication
  19. 2025 Medium

    Revealed an immune-tolerance role: PRDM16 with RORγt defines tolerogenic dendritic cells required for peripheral regulatory T-cell differentiation and oral tolerance.

    Evidence Cell-type-specific PRDM16/RORγt deletion, chromatin/expression profiling, in vivo tolerance models, and human single-cell analysis

    PMID:40228524

    Open questions at the time
    • Direct PRDM16 target genes in tolDCs not defined
    • Whether enzymatic activity is required not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PRDM16's two catalytic activities, its many cofactor complexes, and its layered post-translational modifications are integrated to produce tissue-specific output remains unresolved.
  • No unified model linking H3K9me1 vs H3K4 catalysis to specific gene programs
  • Hierarchy among ubiquitination, sumoylation, and acetylation in vivo not established
  • Genome-wide rules of cofactor selection across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-392499 Metabolism of proteins 3
Partners
CEBPBCTBP1EHMT1MED1PGC1APPARGRBBP4TLE3
Complex memberships
CUL2-APPBP2 E3 ligase complexNuRD complexPRDM16-CtBP repressive complexPRDM16-PGC-1α/β thermogenic complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PRDM16 activates brown fat cell identity by directly binding PGC-1α and PGC-1β through protein-protein interaction, stimulating their transcriptional activity to induce brown fat-selective gene expression including PGC-1alpha, UCP1, and Dio2. Co-immunoprecipitation, shRNA knockdown, ectopic expression in white fat progenitors with measurement of brown fat gene program Cell metabolism High 17618855
2008 PRDM16 controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells: loss of PRDM16 from brown fat precursors promotes muscle differentiation, while ectopic PRDM16 in myoblasts induces brown adipogenesis. PRDM16 stimulates brown adipogenesis by binding to PPARγ and activating its transcriptional function. In vivo fate mapping (Myf5-Cre lineage tracing), shRNA knockdown, ectopic overexpression in myoblasts, Co-immunoprecipitation with PPARγ Nature High 18719582
2008 PRDM16 forms a transcriptional holocomplex containing CtBP-1 and CtBP-2; direct interaction with CtBP selectively mediates repression of white fat-selective genes (e.g., resistin) by recruitment to their promoters. Displacement of CtBP by PGC-1α/PGC-1β allows the PRDM16 complex to activate brown fat genes. Biochemical purification of native PRDM16 complexes from fat cells, Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), genetic absence of CtBP-1/2 Genes & development High 18483224
2009 PRDM16 forms a transcriptional complex with the active form of C/EBP-β (LAP) that is sufficient to initiate the brown fat program from myoblastic precursors and even skin fibroblasts; forced co-expression of PRDM16 and C/EBP-β in fibroblasts generates functional brown fat upon transplantation. Co-immunoprecipitation, mass spectrometry identification of complex components, ectopic co-expression in fibroblasts, in vivo transplantation with PET-FDG imaging Nature High 19641492
2010 Prdm16 is a cell-autonomous determinant of the brown fat-like gene program in subcutaneous white adipocytes; shRNA-mediated depletion of Prdm16 in isolated subcutaneous adipocytes causes a sharp decrease in thermogenic gene expression and a reduction in uncoupled cellular respiration. shRNA knockdown, cellular respiration (uncoupled respiration) measurement, transgenic mouse overexpression The Journal of clinical investigation High 21123942
2012 Prdm3 and Prdm16 are redundant H3K9me1-specific histone methyltransferases (KMTs) that direct cytoplasmic H3K9me1 methylation; this H3K9me1 is converted to H3K9me3 by Suv39h enzymes in the nucleus to reinforce heterochromatin. Simultaneous depletion of both proteins abrogates H3K9me1, prevents H3K9me3, derepresses satellite transcription, and causes disintegration of heterochromatic foci. Biochemical methyltransferase assay, in vivo analysis in mouse embryonic fibroblasts, DNA-FISH, electron microscopy, double knockdown Cell High 22939622
2012 PPARγ full agonists (e.g., rosiglitazone) induce browning of white adipocytes through PRDM16; the mechanism involves increased PRDM16 protein half-life (protein stabilization) rather than transcriptional upregulation. Depletion of PRDM16 blunts the agonist-induced brown fat gene program. shRNA knockdown, protein half-life measurement (cycloheximide chase), in vivo transgenic synergy experiments Cell metabolism High 22405074
2013 EHMT1 (euchromatic histone-lysine N-methyltransferase 1) is an essential component of the PRDM16 transcriptional complex in brown adipose tissue; EHMT1 controls brown adipose cell fate by methylating H3K9me2/3 at muscle-selective gene promoters and also stabilizes PRDM16 protein. Co-immunoprecipitation (EHMT1 in PRDM16 complex), H3K9 methylation analysis, conditional knockout of EHMT1 in adipocytes in vivo, cell fate analysis Nature High 24196706
2013 TLE3 acts as a white-selective cofactor that disrupts the physical interaction between PRDM16 and PPARγ; occupancy of TLE3 and PRDM16 on certain gene promoters is mutually exclusive, and TLE3 suppresses brown-selective genes while inducing white-selective genes. Co-immunoprecipitation (TLE3 disrupts PRDM16-PPARγ interaction), adipose-specific TLE3 transgenic overexpression and knockout mice, gene expression analysis Cell metabolism High 23473036
2014 Prdm16 is dispensable for embryonic BAT development but is required in young mice to suppress white-fat-selective gene expression in BAT through recruitment of the histone methyltransferase Ehmt1. Prdm16 deficiency causes an adult-onset decline in thermogenic character of interscapular BAT. Concurrent deletion of Prdm16 and the closely related Prdm3 accelerates loss of brown fat identity. Brown adipose lineage-specific conditional knockout, gene expression analysis, chromatin recruitment assay (Ehmt1 recruitment), double knockout of Prdm16 and Prdm3 Cell metabolism High 24703692
2014 Adipocyte-specific deletion of PRDM16 markedly inhibits beige adipocyte function in subcutaneous fat and causes subcutaneous adipose tissue to acquire properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation. Fat transplantation experiments confirm PRDM16 is required for metabolic benefits of subcutaneous fat. Adipocyte-specific conditional knockout, cold exposure and β3-agonist treatment, fat transplantation into diet-induced obese mice Cell High 24439384
2015 PRDM16 directly interacts with the MED1 subunit of the Mediator complex through its zinc finger domains; this interaction recruits PRDM16 to the Ucp1 gene enhancer and enhances thyroid hormone receptor (TR)-driven Ucp1 transcription in a Mediator-dependent manner. In vitro binding assay (direct interaction), ChIP recruitment to Ucp1 enhancer, biochemically defined in vitro transcription system, cell-based Ucp1 induction assay with MED1 dependence Genes & development High 25644605
2016 PRDM16 is an H3K4 methyltransferase on chromatin; its N-terminal PR domain harbors intrinsic enzymatic activity, and mutation abolishing this activity prevents suppression of MLL fusion-induced leukemogenesis. PRDM16 methyltransferase activity directly activates Gfi1b, which downregulates the HOXA gene cluster. In vitro histone methyltransferase assay, PR domain mutagenesis, in vitro and in vivo leukemogenesis models, ChIP, shRNA knockdown of Gfi1b Molecular cell High 27151440
2017 PRDM16 suppresses type I interferon-stimulated genes (ISGs) including Stat1 in adipocytes; mechanistically, PRDM16 binds to promoter regions of ISGs and blocks the activating function of IRF1. Prdm16-deficient adipose shows exaggerated type I IFN response and reduced mitochondrial gene expression. ChIP (PRDM16 binding to ISG promoters), shRNA/conditional knockout, ectopic type I IFN activation, in vitro and in vivo gene expression analysis The EMBO journal High 28408438
2018 PRDM16 complex contains GTF2IRD1 as a cold-inducible component that mediates repression of TGF-β-dependent pro-fibrosis genes; PRDM16 recruits EHMT1 and GTF2IRD1 onto promoter/enhancer regions of fibrosis genes to suppress adipose tissue fibrosis independently of UCP1. Biochemical purification of PRDM16 complex (GTF2IRD1 identification), ChIP, adipocyte-selective GTF2IRD1 overexpression and knockout Cell metabolism High 29320702
2018 Cbx4 is a SUMO E3 ligase for Prdm16; Cbx4-mediated sumoylation of Prdm16 at lysine 917 blocks ubiquitination-mediated degradation, stabilizing the protein and enhancing its thermogenic function. This sumoylation also primes Prdm16 to be further stabilized by Ehmt1. SUMO E3 ligase assay, site-directed mutagenesis (K917), ubiquitination assay, Cbx4 knockout mice, Co-immunoprecipitation Cell reports High 29539416
2019 PRDM16-expressing adipocytes secrete β-hydroxybutyrate (BHB), which blocks precursor fibrogenesis and facilitates beige adipogenesis; BHB catabolism in precursor cells via BDH1 is required for beige fat differentiation in vivo. Loss of Prdm16 mimics aging in promoting fibrosis. Conditional Prdm16 knockout, metabolite profiling (BHB secretion), BDH1 knockout in precursor cells, dietary BHB supplementation Cell metabolism High 31155495
2019 PRDM16 is a region-specific transcriptional controller of fatty acid oxidation (FAO) in intestinal crypt progenitors; acute Prdm16 deletion triggers progenitor apoptosis, impaired epithelial differentiation, and intestinal atrophy, and these effects are rescued by acetate treatment. Inducible Prdm16 conditional knockout in intestine, genomic (ChIP-seq/RNA-seq) analysis, enteroid culture with FAO inhibition, acetate rescue Cell stem cell High 31564549
2019 PRDM16 directly interacts with RBBP4 (a NuRD chromatin remodeling complex component) through its N-terminal residues (containing the PR domain); full-length PRDM16 but not the ΔPR isoform associates with NuRD. Crystal structures of PRDM16 N-terminal peptides in complex with RBBP4 show binding within the conserved histone H3-binding groove. Proteomics interactome comparison of full-length vs. ΔPR isoforms, isothermal titration calorimetry (Kd = 3.0 μM), X-ray crystallography of PRDM16 N-terminal peptide–RBBP4 complex Nucleic acids research High 30462309
2021 Prdm16 localizes at the nuclear lamina in fibro-adipogenic progenitors (FAPs), where it cooperates with H3K9 methyltransferases G9a/GLP to mediate tethering and silencing of myogenic genes at the nuclear periphery (lamina-associated domain organization), thereby repressing an alternative myogenic fate. Nuclear fractionation/localization (nuclear envelope), ChIP for H3K9 methylation, lamina-associated domain analysis, genetic/pharmacological disruption of G9a/GLP, in vivo FAP fate analysis Science advances High 34078594
2021 PRDM16 functions as a compact myocardium-enriched transcription factor that activates compact myocardial genes while repressing trabecular myocardial genes in LV compact myocardium; it cooperates with LV-enriched transcription factors Tbx5 and Hand1 for chamber-specific transcriptional regulation. Cardiomyocyte-specific conditional knockout, RNA-seq, ChIP-seq, single-cell RNA-seq, spatial transcriptomics Circulation High 34915728
2022 CUL2-APPBP2 is the ubiquitin E3 ligase that determines PRDM16 protein stability by catalyzing its polyubiquitination; inhibition of CUL2-APPBP2 extends PRDM16 half-life and promotes beige adipocyte biogenesis. Elevated CUL2-APPBP2 in aged adipose tissue degrades PRDM16 and represses thermogenesis. E3 ligase identification (biochemical screen), polyubiquitination assay, protein half-life measurement, adipocyte-specific CUL2-APPBP2 conditional knockout in vivo Nature High 35978186
2022 BCKA-derived acetyl-CoA acetylates PRDM16 at K915, disrupting the interaction between PRDM16 and PPARγ to suppress WAT browning; depletion of BCKA-derived acetyl-CoA robustly promotes WAT browning and energy expenditure. Mass spectrometry identification of acetylation site, site-directed mutagenesis (K915), Co-immunoprecipitation (PRDM16-PPARγ disruption), adipose Bcat2 knockout mice Nature metabolism High 35075301
2007 PRDM16/MEL1 is a Smad3 binding protein in orofacial tissue; the interaction between PRDM16 and Smad3 was confirmed by GST pull-down assay, suggesting a role in modulating TGF-β signaling during orofacial development. Yeast two-hybrid screening, GST pull-down assay, Northern blot and in situ hybridization for expression Biochimica et biophysica acta Medium 17467076
2008 MEL1 (PRDM16) interacts with SKI and stabilizes the inactive Smad3-SKI complex on TGF-β target gene promoters, inhibiting TGF-β signaling; knockdown of both MEL1 and SKI synergistically restored TGF-β responsiveness and reduced tumor growth. Co-immunoprecipitation (MEL1-SKI interaction), ChIP (Smad3-SKI complex on promoters), siRNA knockdown, in vivo tumor growth assay The Journal of biological chemistry Medium 19049980
2003 MEL1S (the short isoform of PRDM16 lacking the PR domain) activates transcription via binding to D2-CONS DNA binding sites; fusion of MEL1 or MEL1S to GAL4 DBD makes them transcriptional repressors. Overexpression of MEL1S (but not full-length MEL1) blocks G-CSF-induced granulocytic differentiation. CASTing (DNA binding consensus identification), reporter gene assays, GAL4 fusion transcription assay, overexpression in IL-3-dependent myeloid cells with G-CSF differentiation assay Blood Medium 12816872
2010 Prdm16 is required for maintenance of hematopoietic and neural stem cells; in neural stem/progenitor cells, Prdm16 binds to the Hgf promoter and regulates its expression. Prdm16 deficiency leads to altered ROS levels and stem cell depletion, partially rescued by HGF or antioxidant (N-acetyl-cysteine) treatment. Germline knockout of Prdm16, ChIP (Prdm16 binding to Hgf promoter), ROS measurement, exogenous HGF rescue, N-acetyl-cysteine treatment in vivo Nature cell biology High 20835244
2017 Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle and for neural stem cell maintenance; Prdm16 is required in neural stem/progenitor cells for expression of Foxj1, a transcription factor that promotes ependymal cell differentiation. Conditional Prdm16 deletion (Nestin-Cre and Nestin-CreERT2), analysis of neural stem cell maintenance, neurogenesis, and ependymal cell formation Genes & development High 28698301
2018 The histone methyltransferase domain of PRDM16 is necessary in radial glia to regulate epigenetic state of transcriptional enhancers and suppress gene expression (e.g., PDZRN3) that controls upper layer cortical neuron position; PRDM16 acts on H3K9 methylation at these enhancers. Conditional Prdm16 deletion in radial glia, ChIP-seq for enhancer epigenetic state, in utero electroporation with methyltransferase-domain mutants, rescue experiments with PDZRN3 Neuron High 29779941
2020 Prdm16 is required for adult long-term HSC quiescence; Prdm16 deletion increases cycling of LT-HSCs and directly regulates Cdkn1a and Egr1 as downstream targets, as shown by ChIP. Inducible conditional Prdm16 knockout (Mx1-Cre), BrdU cell-cycle analysis, ChIP identifying Cdkn1a and Egr1 as direct targets, RNA-seq Proceedings of the National Academy of Sciences of the United States of America Medium 33268499
2020 Cardiac-specific deletion of Prdm16 causes age-dependent cardiac hypertrophy, fibrosis, and mitochondrial dysfunction; Prdm16 and Ehmt factors act together to reduce expression of fetal genes reactivated in hypertrophy by inhibiting the pro-hypertrophic transcription factor Myc. Cardiac-specific conditional knockout, trichrome staining/fibrosis quantification, mitochondrial function assays, gene expression analysis, mechanistic link to Ehmt-Myc axis Cell reports Medium 33086060
2023 PRDM16 binds the promoter of TGFB3 and represses its transcription in cardiomyoblasts; a loss-of-function Q187X variant impairs myocyte proliferation and increases apoptosis associated with transcriptional dysregulation of TGF-β-associated transcripts. ChIP (PRDM16 binding to TGFB3 promoter), luciferase reporter assay, iPSC-derived cardiomyocytes from PRDM16-Q187X proband, CRISPR knock-in mouse model Circulation. Heart failure Medium 38113297
2024 PRDM16 associates with and transcriptionally activates the TRPA1 promoter, suppressing MAPK (P38, ERK1/2) and downstream TGF-β1 expression in renal tubular cells; PRDM16 also directly associates with NRF2 promoter to augment its expression, enhancing GPX4 to suppress ferroptosis. ChIP (PRDM16 binding to TRPA1 and NRF2 promoters), kidney proximal tubule–specific Prdm16 KO and knock-in mice, LPS/CLP sepsis models Redox biology Medium 39549609
2023 PRDM16 binds the promoter of ADAM12 and represses its transcription in vascular smooth muscle cells; Prdm16 deficiency promotes ADAM12-mediated ECM remodeling and VSMC apoptosis, worsening AAA formation. Adam12 knockdown reverses VSMC apoptosis caused by Prdm16 deficiency. ChIP (PRDM16 binding to ADAM12 promoter), VSMC-specific Prdm16 KO mice, periadventitial elastase AAA model, Adam12 knockdown rescue JCI insight Medium 37079380
2024 PRDM16 in VSMCs regulates blood pressure circadian variation; Adra1d (adrenergic receptor α1d) is a transcriptional target of PRDM16. PRDM16 also regulates circadian clock gene Npas2 expression, and its own expression shows a circadian pattern. VSMC-specific Prdm16 KO mice (telemetry BP measurements), mesenteric artery contraction assays, ChIP/promoter analysis for Adra1d, clock gene expression analysis The Journal of clinical investigation Medium 39625782
2017 STAT3 physically interacts with PRDM16 and forms a complex to promote WAT browning; this interaction is downstream of leptin-JAK2-STAT3 signaling mediated by Foxc2. Co-immunoprecipitation (STAT3-PRDM16 complex), chromatin immunoprecipitation, overexpression experiments in adipocytes International journal of obesity Low 28925407
2017 TRPV1 activation induces SIRT1 phosphorylation, which facilitates deacetylation of PRDM16 and promotes its interaction with PPARγ in BAT; PRDM16 acetylation state is modulated by SIRT1 downstream of TRPV1-Ca2+ signaling. In vitro capsaicin treatment with SIRT1 inhibitor/TRPV1 antagonist/BAPTA-AM controls, immunoprecipitation of PRDM16 to assess acetylation, Co-IP of PPARγ-PRDM16 International journal of obesity Low 28104916
2025 PRDM16 and RORγt co-expression defines a novel myeloid antigen-presenting cell subset (PRDM16+RORγt+ tolerizing dendritic cells, tolDCs) required for differentiation of food- and microbiota-specific peripheral regulatory T cells and establishment of oral tolerance; PRDM16 expression is required for tolDC development and function. Conditional genetic perturbation of tolDCs (PRDM16 and RORγt deletion), gene expression/chromatin accessibility profiling, in vivo tolerance models (asthma, food allergy), single-cell analysis of human mesenteric LN/intestine Nature Medium 40228524

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 PRDM16 controls a brown fat/skeletal muscle switch. Nature 1888 18719582
2010 Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. The Journal of clinical investigation 1037 21123942
2007 Transcriptional control of brown fat determination by PRDM16. Cell metabolism 974 17618855
2014 Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 731 24439384
2012 PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell metabolism 647 22405074
2009 Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 606 19641492
2008 Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & development 377 18483224
2014 Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell metabolism 333 24703692
2013 EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 279 24196706
2012 Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 262 22939622
2012 MyomiR-133 regulates brown fat differentiation through Prdm16. Nature cell biology 224 23143398
2016 AMPK/α-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis. Cell metabolism 207 27641099
2019 Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR-133/PRDM16 pathway. International journal of cancer 190 30412280
2019 A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. Cell metabolism 190 31155495
2010 Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress. Nature cell biology 180 20835244
2014 Rice germline-specific Argonaute MEL1 protein binds to phasiRNAs generated from more than 700 lincRNAs. The Plant journal : for cell and molecular biology 158 24635777
2018 Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis. Cell metabolism 146 29320702
2000 A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood 140 11050005
2011 Prdm16 is a physiologic regulator of hematopoietic stem cells. Blood 125 21343612
2013 Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPARγ specifies lipid storage versus thermogenic gene programs. Cell metabolism 123 23473036
2009 Prdm16 is required for normal palatogenesis in mice. Human molecular genetics 122 20007998
2003 A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood 121 12816872
2015 The Multifaceted Roles of PRDM16: Adipose Biology and Beyond. Trends in endocrinology and metabolism: TEM 98 26688472
2022 Post-translational control of beige fat biogenesis by PRDM16 stabilization. Nature 97 35978186
2022 BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16. Nature metabolism 95 35075301
2019 PRDM16 Maintains Homeostasis of the Intestinal Epithelium by Controlling Region-Specific Metabolism. Cell stem cell 88 31564549
2017 TRPV1 activation counters diet-induced obesity through sirtuin-1 activation and PRDM-16 deacetylation in brown adipose tissue. International journal of obesity (2005) 87 28104916
1988 Yeast regulatory gene GAL3: carbon regulation; UASGal elements in common with GAL1, GAL2, GAL7, GAL10, GAL80, and MEL1; encoded protein strikingly similar to yeast and Escherichia coli galactokinases. Molecular and cellular biology 84 3062381
2015 PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1. Genes & development 80 25644605
2021 PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle. Circulation 79 34915728
2008 SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells. The Journal of biological chemistry 75 19049980
1984 Regulation of basal and induced levels of the MEL1 transcript in Saccharomyces cerevisiae. Molecular and cellular biology 72 6209559
2021 l-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice. Diabetes 71 33863801
2020 Prdm16 Deficiency Leads to Age-Dependent Cardiac Hypertrophy, Adverse Remodeling, Mitochondrial Dysfunction, and Heart Failure. Cell reports 68 33086060
2017 PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing. The EMBO journal 63 28408438
2017 Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells. Genes & development 61 28698301
2020 The conserved and divergent roles of Prdm3 and Prdm16 in zebrafish and mouse craniofacial development. Developmental biology 59 32044379
2014 Gcn5 and PCAF regulate PPARγ and Prdm16 expression to facilitate brown adipogenesis. Molecular and cellular biology 57 25071153
2018 The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position. Neuron 55 29779941
2016 PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity. Molecular cell 55 27151440
2024 PRDM16 suppresses ferroptosis to protect against sepsis-associated acute kidney injury by targeting the NRF2/GPX4 axis. Redox biology 54 39549609
2008 RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Blood 53 18202228
2025 PRDM16-dependent antigen-presenting cells induce tolerance to gut antigens. Nature 51 40228524
2005 Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). Genes, chromosomes & cancer 51 16015645
1985 Analysis of the inducible MEL1 gene of Saccharomyces carlsbergensis and its secreted product, alpha-galactosidase (melibiase). Gene 51 3000884
2021 Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair. Science advances 50 34078594
2009 PRDM16: the interconvertible adipo-myocyte switch. Trends in cell biology 49 19285866
1985 The nucleotide sequence of the yeast MEL1 gene. Nucleic acids research 48 2997745
2022 PRDM16 Regulating Adipocyte Transformation and Thermogenesis: A Promising Therapeutic Target for Obesity and Diabetes. Frontiers in pharmacology 44 35462933
2018 Obesity-Associated miR-199a/214 Cluster Inhibits Adipose Browning via PRDM16-PGC-1α Transcriptional Network. Diabetes 44 30279164
2015 Functions of Prdm16 in thermogenic fat cells. Temperature (Austin, Tex.) 43 27227007
2007 PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue. Biochimica et biophysica acta 43 17467076
2016 Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex. Development (Cambridge, England) 42 27993981
1990 A new family of polymorphic genes in Saccharomyces cerevisiae: alpha-galactosidase genes MEL1-MEL7. Molecular & general genetics : MGG 42 1980522
2019 PRDM16 functions as a suppressor of lung adenocarcinoma metastasis. Journal of experimental & clinical cancer research : CR 40 30683132
2017 Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice. International journal of obesity (2005) 40 28925407
2023 PRDM16 exerts critical role in myocardial metabolism and energetics in type 2 diabetes induced cardiomyopathy. Metabolism: clinical and experimental 39 37433344
2015 Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway. International journal of obesity supplements 39 27152168
2013 Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity. Histology and histopathology 39 23771475
2022 SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 37 36451857
2000 Physiological studies in aerobic batch cultivations of Saccharomyces cerevisiae strains harboring the MEL1 gene. Biotechnology and bioengineering 37 10745193
2018 PRDM16 isoforms differentially regulate normal and leukemic hematopoiesis and inflammatory gene signature. The Journal of clinical investigation 36 29878897
2007 Leukemogenesis of the EVI1/MEL1 gene family. International journal of hematology 35 17483069
2018 Cbx4 Sumoylates Prdm16 to Regulate Adipose Tissue Thermogenesis. Cell reports 34 29539416
2017 Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation. Nature communications 34 28701693
2020 Prdm16 is a critical regulator of adult long-term hematopoietic stem cell quiescence. Proceedings of the National Academy of Sciences of the United States of America 32 33268499
2018 MiR-499/PRDM16 axis modulates the adipogenic differentiation of mouse skeletal muscle satellite cells. Human cell 32 30097922
2016 PRDM16 is associated with evasion of apoptosis by prostatic cancer cells according to RNA interference screening. Molecular medicine reports 32 27511603
2011 Novel SNPs in the PRDM16 gene and their associations with performance traits in chickens. Molecular biology reports 32 21761141
2016 miR-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells. Oncotarget 31 26701852
2014 Methylation of PRDM2, PRDM5 and PRDM16 genes in lung cancer cells. International journal of clinical and experimental pathology 31 24966940
2019 Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex. Nucleic acids research 30 30462309
2012 Double Myod and Igf2 inactivation promotes brown adipose tissue development by increasing Prdm16 expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 22859371
2017 Gelidium elegans Regulates the AMPK-PRDM16-UCP-1 Pathway and Has a Synergistic Effect with Orlistat on Obesity-Associated Features in Mice Fed a High-Fat Diet. Nutrients 29 28358328
2005 MEL1S, not MEL1, is overexpressed in myelodysplastic syndromes patients with t(1;3)(p36;q21). Leukemia research 29 16102824
2020 Cardiac-specific inactivation of Prdm16 effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes. American journal of physiology. Heart and circulatory physiology 28 32083975
2016 A wide reprogramming of histone H3 modifications during male meiosis I in rice is dependent on the Argonaute protein MEL1. Journal of cell science 27 27521428
2009 PRDM16 expression in the developing mouse embryo. Acta histochemica 27 19853285
2020 PRDM16 orchestrates angiogenesis via neural differentiation in the developing brain. Cell death and differentiation 25 32015502
2004 Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells. Oncogene 25 14712237
2023 Discovery of PRDM16-Mediated TRPA1 Induction as the Mechanism for Low Tubulo-Interstitial Fibrosis in Diabetic Kidney Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 38072665
2014 Downregulation of Prdm16 mRNA is a specific antileukemic mechanism during HOXB4-mediated HSC expansion in vivo. Blood 22 25082879
2023 PRDM16 deficiency in vascular smooth muscle cells aggravates abdominal aortic aneurysm. JCI insight 21 37079380
2018 HDAC3-Selective Inhibition Activates Brown and Beige Fat Through PRDM16. Endocrinology 21 29757434
2021 PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors. Development (Cambridge, England) 20 33597191
2010 Two novel SNPs in the coding region of the bovine PRDM16 gene and its associations with growth traits. Molecular biology reports 20 19760096
2024 Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure. The Journal of clinical investigation 19 39625782
2022 Withaferin A Promotes White Adipose Browning and Prevents Obesity Through Sympathetic Nerve-Activated Prdm16-FATP1 Axis. Diabetes 19 34732538
2015 Role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during transdifferentiation of C2C12 cells. Gene 19 26071185
2003 Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1. Genes, chromosomes & cancer 19 12557231
2020 Cardiomyopathy due to PRDM16 mutation: First description of a fetal presentation, with possible modifier genes. American journal of medical genetics. Part C, Seminars in medical genetics 18 31965688
2024 PRDM16-DT is a novel lncRNA that regulates astrocyte function in Alzheimer's disease. Acta neuropathologica 17 39207536
2022 Population genomics reveals that natural variation in PRDM16 contributes to cold tolerance in domestic cattle. Zoological research 17 35238185
2021 Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 17 34330825
2019 EDAR, LYPLAL1, PRDM16, PAX3, DKK1, TNFSF12, CACNA2D3, and SUPT3H gene variants influence facial morphology in a Eurasian population. Human genetics 17 31025105
2003 Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia. Experimental hematology 17 14585371
2024 LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance. Theranostics 16 38855188
2017 The Transcription Factor Prdm16 Marks a Single Retinal Ganglion Cell Subtype in the Mouse Retina. Investigative ophthalmology & visual science 16 29053761
2024 Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators. Cardiovascular research 14 37842925
2023 Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice. Circulation. Heart failure 14 38113297

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