Affinage

SETDB2

Histone-lysine N-methyltransferase SETDB2 · UniProt Q96T68

Length
719 aa
Mass
81.9 kDa
Annotated
2026-06-10
35 papers in source corpus 27 papers cited in narrative 27 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

SETDB2 (CLLD8/KMT1F) is a SET-domain histone H3 lysine 9 (H3K9) trimethyltransferase that establishes repressive H3K9me3 chromatin at defined promoters to silence transcription, acting most prominently as a brake on inflammatory and developmental gene programs (PMID:20404330, PMID:25419628, PMID:31350176). At constitutive heterochromatin it methylates H3K9 at interspersed repeats and centromere-associated sequences, recruits HP1, and is required for centromere protein loading and timely mitosis, working together with SUV39H1 (PMID:20404330). In innate immunity, SETDB2 is induced downstream of type I interferon (IFNβ) via JAK/STAT3 signaling and deposits H3K9me3 at NF-κB binding sites on cytokine and chemokine promoters (e.g. Cxcl1), restraining inflammation and enabling the inflammatory-to-reparative macrophage transition (PMID:25419628, PMID:31350176, PMID:34479991); STAT3 both drives SETDB2 expression and, paradoxically, binds SETDB2 to limit its interaction with RELA, thereby tuning NF-κB output (PMID:39435663). This IFNβ–SETDB2 axis governs macrophage and fibroblast behavior across diabetic wound healing, atherosclerosis, and aortic aneurysm, where SETDB2 silences targets including TIMP1-3 and modulates xanthine oxidase and macrophage polarization (PMID:31350176, PMID:34003795, PMID:37325923, PMID:38905784). SETDB2 functions as a recurrent transcriptional repressor in cancer and disease by trimethylating promoters of tumor suppressors and stress regulators — WWOX, CADM1, CDKN2C, NRF2, TFRC, SRSF1, Smad3 and IDE — with cell-type-specific upstream activators such as E2A-PBX1 and TCF21 (PMID:27572307, PMID:29694893, PMID:36504353, PMID:41316884, PMID:40645600, PMID:41880325). In zebrafish it patterns the embryonic axis by restricting the dorsal organizer and convergent-extension movements through suppression of fgf8 and dvr1 signaling (PMID:20133783, PMID:24892953). Beyond catalysis, SETDB2 also acts non-enzymatically: it binds BUBR1 to promote CDC20–APC/C assembly and CYCLIN B1 degradation for accurate chromosome segregation, and it can positively regulate inflammatory/glycolytic genes via enhancer-promoter looping independent of its methyltransferase activity (PMID:38151757, PMID:40166182). Consistent with a protein-interaction role, its annotated methyl-CpG-binding domain does not bind DNA but mediates binding to C11orf46 (PMID:38458157).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Low

    Defining SETDB2's domain architecture first raised the hypothesis that it acts in methylation-dependent transcriptional repression.

    Evidence Sequence/domain analysis identifying MBD, preSET, and SET domains at 13q14

    PMID:11306461

    Open questions at the time
    • Computational prediction only, no enzymatic or functional assay
    • Catalytic substrate not demonstrated
    • MBD DNA-binding inferred but not tested
  2. 2010 High

    Established SETDB2 as a bona fide H3K9 trimethyltransferase at heterochromatin required for mitotic fidelity, moving it from predicted to functional enzyme.

    Evidence siRNA knockdown, ChIP for H3K9me3 at repeats/centromeres, HP1 and CENP localization, cell cycle timing

    PMID:20404330

    Open questions at the time
    • Did not resolve direct versus indirect H3K9me3 deposition in vitro
    • Relationship between heterochromatin and gene-specific roles unclear
    • Mechanism of HP1 recruitment not dissected
  3. 2010 High

    Showed SETDB2 controls vertebrate body-axis patterning by acting upstream of Fgf8, the first developmental function in vivo.

    Evidence Morpholino knockdown in zebrafish with mRNA and dominant-negative FGFR rescue, in situ hybridization

    PMID:20133783

    Open questions at the time
    • Whether fgf8 repression is via direct promoter H3K9me3 not shown
    • Catalytic dependence not tested in this system
    • Mammalian developmental relevance untested
  4. 2014 High

    Defined SETDB2 as an IFN-induced epigenetic brake on NF-κB target genes, linking type I IFN signaling to chromatin repression of inflammation.

    Evidence Hypomorphic gene-trap mice, ChIP for H3K9me3 at Cxcl1, neutrophil quantification, superinfection model; plus zebrafish dvr1 epistasis

    PMID:24892953 PMID:25419628

    Open questions at the time
    • How IFN induces SETDB2 transcription not mapped
    • Recruitment to specific NF-κB promoters undefined
    • Direct enzymatic vs scaffolding contribution not separated
  5. 2016 High

    Extended SETDB2 to metabolic and oncogenic gene silencing, showing it represses lipid-synthesis regulators and tumor suppressors via promoter H3K9me3.

    Evidence ChIP, chromatin looping, knockdown in hepatocytes/ob/ob mice (Insig2a/SREBP); ChIP/knockdown in gastric cancer (WWOX, CADM1)

    PMID:27568546 PMID:27572307

    Open questions at the time
    • Targeting specificity to individual promoters unexplained
    • Whether GR-SETDB2 cooperation is direct binding unknown
    • Generality of tumor-suppressor silencing across cancers untested
  6. 2018 High

    Placed SETDB2 within defined oncogenic transcriptional circuits as an effector silencing cell-cycle inhibitors.

    Evidence ChIP for H3K9me3 at CDKN2C, shRNA in vitro/xenograft, E2A-PBX1 promoter binding; monocyte KO/overexpression in superinfection

    PMID:29694893 PMID:29749709

    Open questions at the time
    • E2A-PBX1 → SETDB2 induction mechanism not fully resolved
    • Direct recruitment to CDKN2C promoter not shown
    • Breadth of repressed loci undefined
  7. 2019 High

    Demonstrated through cell-type-specific deletion that the IFNβ–SETDB2 axis governs macrophage phenotype transitions and is dysregulated in diabetes.

    Evidence Myeloid-specific Setdb2 KO mice, ChIP for H3K9me3 at NF-κB sites, IFNβ treatment, human/murine wound macrophages

    PMID:30670717 PMID:31350176

    Open questions at the time
    • Molecular basis of impaired IFNβ-SETDB2 axis in diabetes unclear
    • How SETDB2 selects NF-κB-bound promoters unknown
    • Xanthine oxidase regulation mechanism not detailed
  8. 2020 Medium

    Revealed a non-histone substrate and protein-stabilizing role, broadening SETDB2's catalytic repertoire beyond histones.

    Evidence Co-IP, in vitro methylation of ΔNp63α, shRNA, mammosphere and tumor-initiation rescue

    PMID:32549764

    Open questions at the time
    • Methylation site on ΔNp63α not mapped
    • Mechanism of methylation-dependent stabilization unclear
    • Single-lab observation
  9. 2021 High

    Confirmed in vivo that loss of SETDB2 unleashes vascular and infection-driven inflammation, establishing protective anti-inflammatory function across disease contexts.

    Evidence Myeloid-specific KO mice, scRNA-Seq, ChIP, JAK/STAT manipulation, human SARS-CoV-2 and atherosclerosis samples

    PMID:34003795 PMID:34479991

    Open questions at the time
    • Why coronavirus lowers IFNβ-JAK1/STAT3-SETDB2 signaling unresolved
    • Efferocytosis defect mechanism not pinned to specific targets
    • M1-restricted induction mechanism unknown
  10. 2023 High

    Mapped a specific repressed target program (TIMP1-3) linking SETDB2 loss to matrix remodeling disease, and validated pharmacologic JAK modulation of SETDB2.

    Evidence Myeloid-specific KO, scRNA-Seq, ChIP at TIMP1-3, AAA model, Tofacitinib; NRF2 ChIP/functional work in LUAD

    PMID:36504353 PMID:37325923

    Open questions at the time
    • Promoter-selection determinants for TIMP genes unknown
    • Whether JAK inhibition acts solely through SETDB2 unclear
    • NRF2 axis is medium-confidence single lab
  11. 2024 High

    Defined a methyltransferase-independent mitotic role and a paradoxical STAT3 partnership, separating SETDB2's enzymatic and scaffolding functions.

    Evidence Reciprocal Co-IP (BUBR1, CDC20-APC/C; STAT3-SETDB2, SETDB2-RELA), catalytic-dead mutants, ATAC/RNA-Seq, CYCLIN B1 degradation assays

    PMID:38151757 PMID:38458157 PMID:38905784 PMID:39435663

    Open questions at the time
    • Structural basis of SETDB2-BUBR1 and SETDB2-RELA contacts undefined
    • How STAT3 both induces and inhibits SETDB2 spatially/temporally unclear
    • MBD-C11orf46 interaction functional consequence not established
  12. 2025 High

    Expanded SETDB2 to a broad disease-relevant repressor acting on splicing, iron metabolism, fibrosis, kidney, and trained-immunity programs through both catalytic and looping mechanisms.

    Evidence Cell-type-specific KO/KD models with ChIP at Smad3, TFRC, SRSF1, IDE, ALPK1; TCF21/KLF4 promoter assays; chromosome conformation and catalytic-dead analysis

    PMID:40166182 PMID:40645600 PMID:41277557 PMID:41316884 PMID:41482828 PMID:41880325 PMID:41946995

    Open questions at the time
    • Determinants directing SETDB2 to such diverse promoters unknown
    • Balance between repressive H3K9me3 and activating looping not generalized
    • Several axes from single-lab studies awaiting replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SETDB2 achieves locus and substrate specificity — selecting particular NF-κB, tumor-suppressor, and metabolic promoters versus deploying its non-enzymatic looping/scaffolding activity — remains unresolved.
  • No unifying model for promoter targeting
  • Switch between catalytic repression and enhancer-promoter looping undefined
  • Structural data on SETDB2 complexes limited

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2
Partners
BUBR1C11ORF46CDC20RELASTAT3SUV39H1TP63
Complex memberships
APC/C (functional association via BUBR1/CDC20)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SETDB2 (CLLD8) contains a methyl-CpG binding domain, a preSET domain, and a SET domain, suggesting it functions in methylation-mediated transcriptional repression; identified as a novel gene at chromosome 13q14. Sequence analysis and domain characterization Cancer research Low 11306461
2010 SETDB2/CLLD8/KMT1F catalyzes trimethylation of histone H3K9 at interspersed repetitive elements and centromere-associated repeats, recruits heterochromatin protein 1 (HP1) to centromeres, and its depletion causes loss of CENP proteins and delayed mitosis, establishing a role in chromosome condensation and segregation. It acts in concert with SUV39H1/KMT1A. siRNA knockdown, ChIP, immunofluorescence, cell cycle analysis The Journal of biological chemistry High 20404330
2010 In zebrafish, Setdb2 (H3K9 methyltransferase) restricts dorsal organizer territory and regulates left-right asymmetry by suppressing fgf8 expression; knockdown expands organizer markers and increases fgf8 mRNA, and these defects are rescued by dominant-negative FGF receptor or fgf8 knockdown, placing Setdb2 upstream of Fgf8 signaling. Morpholino knockdown in zebrafish embryos, mRNA rescue, dominant-negative receptor epistasis, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America High 20133783
2014 In influenza-infected mice, Setdb2 expression is induced by type I interferon signaling; Setdb2 occupies the Cxcl1 promoter and is required for H3K9me3 deposition there, repressing CXCL1 and other NF-κB target genes; hypomorphic Setdb2 mice show increased neutrophil infiltration and reduced susceptibility to bacterial superinfection, placing Setdb2 as a crosstalk mediator between type I IFN and NF-κB pathways. Gene-trap hypomorphic mouse model, ChIP (H3K9me3 at Cxcl1 promoter), gene expression analysis, neutrophil infiltration quantification Nature immunology High 25419628
2014 In zebrafish, Setdb2 regulates convergence and extension (C&E) movements during gastrulation by transcriptionally suppressing dvr1 (a TGF-β ligand) to an appropriate level; both knockdown and overexpression of dvr1 phenocopy C&E defects, placing Setdb2-dvr1 as a critical transcriptional cascade for body axis formation. Morpholino knockdown, epistasis rescue experiments, in situ hybridization in zebrafish embryos Developmental biology Medium 24892953
2016 SETDB2 is induced by glucocorticoid receptor (GR) signaling in liver; it facilitates GR chromatin enrichment and glucocorticoid-dependent enhancer-promoter interactions at the Insig2a locus, thereby inducing Insig2a expression during fasting; Insig2a in turn represses SREBP and limits lipid synthesis. SETDB2 knockdown prevents glucocorticoid-mediated inhibition of SREBP processing. ChIP, chromatin conformation (enhancer-promoter looping), siRNA knockdown in hepatocytes and in vivo, glucocorticoid treatment of ob/ob mice Cell metabolism High 27568546
2016 SETDB2 catalyzes H3K9me3 at the promoter regions of tumor suppressor genes WWOX and CADM1 in gastric cancer cells, repressing their transcription; ectopic SETDB2 protein is recruited to these promoters as shown by ChIP, and SETDB2 knockdown reduces global H3K9me3 and de-represses these genes. ChIP (H3K9me3), siRNA knockdown, microarray gene expression, SETDB2 overexpression Oncotarget Medium 27572307
2018 SETDB2 is a direct transcriptional target of the E2A-PBX1 chimeric transcription factor in pre-BCR+ ALL; SETDB2 in turn deposits H3K9me3 at the CDKN2C promoter to repress this cell-cycle inhibitor, creating an oncogenic pathway downstream of E2A-PBX1 that silences a tumor suppressor. ChIP (H3K9me3 at CDKN2C promoter), shRNA knockdown in vitro and in vivo (xenograft), promoter analysis for E2A-PBX1 binding Cell reports High 29694893
2018 In monocytes during systemic bacterial infection, elevated Setdb2 represses antifungal immunity genes (including Il1b, Tnf, Il6, Ifnb, Cxcl1) via H3K9 methylation at their promoters, promoting susceptibility to secondary Candida albicans super-infection; lentiviral Setdb2 knockout reverses this repression. Lentivirus-mediated Setdb2 knockout and overexpression in monocytes, gene expression analysis, murine super-infection model Cellular microbiology Medium 29749709
2019 In wound macrophages, SETDB2 trimethylates histone H3 (H3K9me3) at NF-κB binding sites on inflammatory cytokine gene promoters to suppress their transcription; SETDB2 expression is regulated by IFNβ, and myeloid-specific deletion of Setdb2 impairs transition from inflammatory to reparative macrophage phenotype; under diabetic conditions the IFNβ-Setdb2 axis is impaired. Additionally, SETDB2 regulates xanthine oxidase expression and thus uric acid production. Myeloid-specific Setdb2 knockout mice, ChIP (H3K9me3 at NF-κB sites), IFNβ treatment, wound macrophage isolation from diabetic patients and controls Immunity High 31350176
2019 In influenza-associated encephalopathy, Setdb2 is upregulated in brain tissue and deposits H3K9me3 at the Caveolin-1 promoter to repress Caveolin-1 expression, contributing to blood-brain barrier breakdown; ChIP confirmed H3K9 methylation at the Caveolin-1 promoter. Murine IAE model (LPS + influenza), ChIP (H3K9me3 at Caveolin-1 promoter), gene expression profiling of 84 histone modification enzymes Scientific reports Medium 30670717
2020 SETDB2 interacts with and methylates ΔNp63α protein, stabilizing it; SETDB2 also upregulates transcription of ΔNp63α downstream Hedgehog pathway genes; SETDB2 knockdown reduces breast cancer stem cell population and mammosphere formation, and restoring ΔNp63α rescues the defect. Co-immunoprecipitation (SETDB2–ΔNp63α interaction), in vitro methylation assay, shRNA knockdown, mammosphere formation assay, in vivo tumor initiation International journal of biological sciences Medium 32549764
2021 Coronavirus infection decreases SETDB2 in macrophages via reduction of IFNβ-JAK1/STAT3 signaling; decreased SETDB2 reduces H3K9me3 at NF-κB binding sites on inflammatory gene promoters, increasing macrophage-mediated inflammation; IFNβ treatment restores SETDB2 and represses inflammation; myeloid-specific Setdb2 KO mice show enhanced pathologic inflammation after coronavirus infection. Myeloid-specific Setdb2 KO mice, JAK/STAT pathway blockade, ChIP (H3K9me3 at NF-κB sites), IFNβ treatment, human SARS-CoV-2 patient monocytes Proceedings of the National Academy of Sciences of the United States of America High 34479991
2021 SETDB2 deficiency in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis; loss of SETDB2 in macrophages leads to increased monocyte populations, enhanced inflammatory gene expression, macrophage accumulation in plaques, and attenuated efferocytosis; SETDB2 expression is upregulated in M1 but not M2 macrophages. Bone marrow transplantation into Ldlr-KO mice, single-cell RNA-Seq of atherosclerotic plaque cells, flow cytometry, efferocytosis assay JCI insight High 34003795
2022 SETDB2 deposits H3K9me3 at the NRF2 promoter to suppress NRF2 transcription in lung adenocarcinoma cells; reduced SETDB2 activates NRF2 and its downstream targets (NQO1, FTH1, ME1), promotes malignant processes, and reduces ROS-induced apoptosis; SETDB2 overexpression suppresses tumor progression in vivo and sensitizes cells to chemotherapy. ChIP-qPCR (H3K9me3 at NRF2 promoter), shRNA/overexpression in LUAD cells, in vivo tumor assay, GSEA Cancer medicine Medium 36504353
2023 In aortic macrophages, IFNβ regulates SETDB2 expression via JAK/STAT signaling; SETDB2 deposits H3K9me3 at TIMP1-3 gene promoters to suppress TIMP1-3 transcription, leading to unregulated MMP activity; myeloid-specific Setdb2 KO mice are protected from AAA formation with increased TIMP expression and preserved aortic architecture; JAK/STAT inhibitor Tofacitinib limits SETDB2 expression in aortic macrophages. Myeloid-specific Setdb2 KO mice, scRNA-Seq, ChIP (H3K9me3 at TIMP1-3 promoters), angiotensin II/high-fat diet AAA model, pharmacologic JAK inhibition Annals of surgery High 37325923
2024 SETDB2 interacts with BUBR1 and is required for CDC20 binding to BUBR1 and to the APC/C complex, and for CYCLIN B1 degradation to ensure accurate chromosome segregation and mitosis; these functions are independent of SETDB2's histone methyltransferase activity. Co-immunoprecipitation (SETDB2–BUBR1, CDC20–BUBR1/APC/C interactions), methyltransferase-dead mutant analysis, CYCLIN B1 degradation assay, mitosis assays FEBS open bio Medium 38151757
2024 STAT3 is required for SETDB2 expression in macrophages; paradoxically, STAT3 also acts as a binding partner of SETDB2 and represses SETDB2 activity by inhibiting its interaction with the NF-κB component RELA, leading to increased NF-κB-mediated inflammatory gene expression; SETDB2 suppresses inflammatory gene programs by inhibiting chromatin accessibility at NF-κB-dependent promoters; STAT3/SETDB2 binding is increased in diabetic wound macrophages. ATAC-Seq, RNA-Seq of myeloid-specific Setdb2 and STAT3 KO wound macrophages, Co-immunoprecipitation (STAT3–SETDB2, SETDB2–RELA interactions) JCI insight High 39435663
2024 The annotated methyl-CpG-binding domain (MBD) of SETDB2 does not bind DNA but instead functions as a protein-protein interaction domain that binds a cystine-rich domain of C11orf46, as determined by structural characterization. Structural characterization of MBD domain (referenced crystallographic/structural study by Mahana et al.) Structure Medium 38458157
2025 TNF-α increases Setdb2 expression in fibroblasts via JAK1,3/STAT3 signaling; elevated SETDB2 represses fibroblast-to-myofibroblast transition; pharmacologic or genetic inhibition of JAK1,3/STAT3 reduces Setdb2 and improves myofibroblast gene expression; fibroblast-specific SETDB2 knockdown improves diabetic wound repair. Murine transgenic models, JAK inhibitor treatment, fibroblast-specific SETDB2 knockdown, TNF-α receptor blockade, macrophage supernatant stimulation JCI insight High 41277557
2025 SETDB2 regulates macrophage trained immunity through two distinct mechanisms: (1) positively regulating glycolytic and inflammatory pathway genes via enhancer-promoter chromatin looping independently of its H3K9 methyltransferase activity; (2) depositing H3K9me3 at promoters to repress interferon response pathway genes. Only mechanism (1) operates in response to sterile inflammatory stimuli, while both operate in response to pathogenic (β-glucan) training. Genetic mouse models, genomic analysis (ChIP, chromosome conformation), methyltransferase-dead mutant, β-glucan and Western diet/oxLDL trained immunity models bioRxivpreprint Medium 40166182
2025 SETDB2 deposits H3K9me3 at the Smad3 promoter in podocytes, repressing SMAD3 expression and activation to preserve podocyte function in diabetic kidney disease; TCF21 is identified as a direct upstream transcriptional activator of Setdb2 by binding to its promoter; podocyte-specific SETDB2 deficiency accelerates DKD progression. Podocyte-specific Setdb2 KO mice, ChIP (H3K9me3 at Smad3 promoter), promoter binding assay for TCF21, human DKD patient glomerular samples Advanced science High 41316884
2025 SETDB2 deposits H3K9me3 at two sites in the TFRC promoter, repressing TFRC expression; this suppresses the TFRC-STEAP3-DMT1 iron uptake axis, modulating cellular Fe2+ and ROS levels in esophageal squamous cell carcinoma; TFRC knockdown rescues proliferation changes caused by SETDB2 knockdown, placing TFRC as an essential mediator downstream of SETDB2. ChIP (H3K9me3 at TFRC promoter), shRNA knockdown, Fe2+/ROS measurement, rescue experiments, in vivo tumor models Biochemical pharmacology Medium 40645600
2026 SETDB2 deposits H3K9me3 at the SRSF1 promoter, repressing SRSF1 (splicing factor) expression; reduced SRSF1 decreases the proportion of functional (tumor-suppressive) SHP-1 splice forms, leading to sustained JAK/STAT3 activation and enhanced tumor immunosuppression in hepatocellular carcinoma; this SETDB2/SRSF1/SHP-1/STAT3 axis drives immune escape. ChIP (H3K9me3 at SRSF1 promoter), SETDB2 KD functional experiments, PDX model comparison (responders vs. non-responders), RNA-seq + proteomics Oncogene Medium 41946995
2026 SETDB2 upregulation in trigeminal ganglion neurons deposits H3K9me3 and blocks KLF4 transcription factor binding to the IDE (insulin-degrading enzyme) promoter, suppressing IDE expression and impairing CGRP degradation; this leads to increased CGRP levels and migraine-like pain behaviors; reversing SETDB2 upregulation reduces H3K9me3 and alleviates pain. Nitroglycerin-induced chronic migraine mouse model, ChIP (H3K9me3 at IDE promoter, KLF4 binding assay), SETDB2 overexpression/knockdown in TG neurons, human CSF SETDB2 measurement Cell reports Medium 41880325
2026 SETDB2 knockdown in macrophages reduces H3K9me3 and upregulates ALPK1 expression; ALPK1 overexpression reverses the M2-polarizing and chondroprotective effects of SETDB2 overexpression, establishing ALPK1 as a direct H3K9me3-regulated downstream target of SETDB2 that controls macrophage polarization in knee osteoarthritis. ChIP-qPCR (H3K9me3 at ALPK1 promoter), shRNA knockdown, SETDB2 overexpression, co-culture experiments, KOA mouse model FASEB journal Medium 41482828
2024 Setdb2 KO in macrophages promotes M2 polarization through upregulation of PI3K/Akt signaling; PI3K inhibitor LY294002 nullifies the M2-polarizing effect of Setdb2 KO, placing Setdb2 as a repressor of PI3K/Akt-driven alternative macrophage activation. Conditional Setdb2 KO in mice, BMDM culture, RNA sequencing, Western blotting, PI3K inhibitor treatment Biochemical and biophysical research communications Medium 38905784

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The Histone Methyltransferase Setdb2 Modulates Macrophage Phenotype and Uric Acid Production in Diabetic Wound Repair. Immunity 124 31350176
2014 The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nature immunology 120 25419628
2001 Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell chronic lymphocytic leukemia. Cancer research 84 11306461
2019 Emerging roles of H3K9me3, SETDB1 and SETDB2 in therapy-induced cellular reprogramming. Clinical epigenetics 71 30850015
2010 CLLD8/KMT1F is a lysine methyltransferase that is important for chromosome segregation. The Journal of biological chemistry 67 20404330
2016 SETDB2 Links Glucocorticoid to Lipid Metabolism through Insig2a Regulation. Cell metabolism 57 27568546
2010 Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry through suppressing fgf8 activity. Proceedings of the National Academy of Sciences of the United States of America 44 20133783
2021 Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2. Proceedings of the National Academy of Sciences of the United States of America 32 34479991
2021 Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis. JCI insight 29 34003795
2018 SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression. Cell reports 29 29694893
2016 Oncogenic roles of the SETDB2 histone methyltransferase in gastric cancer. Oncotarget 28 27572307
2014 Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1. Developmental biology 19 24892953
2023 The Histone Methyltransferase SETDB2 Modulates Tissue Inhibitors of Metalloproteinase-Matrix Metalloproteinase Activity During Abdominal Aortic Aneurysm Development. Annals of surgery 16 37325923
2019 Abrogated Caveolin-1 expression via histone modification enzyme Setdb2 regulates brain edema in a mouse model of influenza-associated encephalopathy. Scientific reports 15 30670717
2024 The STAT3/SETDB2 axis dictates NF-κB-mediated inflammation in macrophages during wound repair. JCI insight 14 39435663
2015 Left-Right Axis Differentiation and Functional Lateralization: a Haplotype in the Methyltransferase Encoding Gene SETDB2 Might Mediate Handedness in Healthy Adults. Molecular neurobiology 14 26572639
2020 SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein. International journal of biological sciences 11 32549764
2023 THE CRITICAL ROLE OF THE HISTONE MODIFICATION ENZYME SETDB2 IN THE PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME. Shock (Augusta, Ga.) 7 37195726
2017 The SETDB2 locus: evidence for a genetic link between handedness and atopic disease. Heredity 7 29234167
2015 A functional AT/G polymorphism in the 5'-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14. Genes and immunity 7 26378653
2022 Histone lysine methyltransferase SETDB2 suppresses NRF2 to restrict tumor progression and modulates chemotherapy sensitivity in lung adenocarcinoma. Cancer medicine 6 36504353
2024 Downregulation of Setdb2 promotes alternative activation of macrophages via the PI3K/Akt pathway to attenuate NAFLD after sleeve gastrectomy. Biochemical and biophysical research communications 4 38905784
2020 Oncogenic Roles Of A Histone Methyltransferase SETDB2 In AML1-ETO Positive AML. Cancer management and research 4 32099474
2018 Bacteria-induced susceptibility to Candida albicans super-infection in mice via monocyte methyltransferase Setdb2. Cellular microbiology 4 29749709
2025 Setdb2 Regulates Inflammatory Trigger-Induced Trained Immunity of Macrophages Through Two Different Epigenetic Mechanisms. bioRxiv : the preprint server for biology 2 40166182
2026 SETDB2 Alleviates Knee Osteoarthritis Progression by Promoting M2-Like Macrophage Polarization via Targeting ALPK1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41482828
2025 Setdb2 Regulates Inflammatory Trigger-Induced Trained Immunity of Macrophages Through Two Different Epigenetic Mechanisms. Research square 1 40502770
2025 SETDB2 participates in iron metabolism in esophageal squamous cell carcinoma via H3K9me3-mediated TFRC silencing. Biochemical pharmacology 1 40645600
2025 TNF-α represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2. JCI insight 1 41277557
2025 SETDB2 Mitigates Podocyte Dysfunction in Diabetic Kidney Disease Through Epigenetic Silencing of SMAD3. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41316884
2024 SETDB2 interacts with BUBR1 to induce accurate chromosome segregation independently of its histone methyltransferase activity. FEBS open bio 1 38151757
2024 One form and two functions: MBD of SETDB2 is a protein-interacting domain. Structure (London, England : 1993) 1 38458157
2026 SETDB2-mediated transcriptional repression of IDE in sensory neurons promotes migraine-like pain behaviors in mice. Cell reports 0 41880325
2026 SETDB2 induces abnormal SHP-1 splicing and promotes immunosuppression in hepatocellular carcinoma. Oncogene 0 41946995
2026 Casticin promotes M2 macrophage polarisation and dorsal root ganglion neuronal autophagy to alleviate cold hyperalgesia in knee osteoarthritis by regulating histone-lysine N-methyltransferase (SETDB2). British journal of pharmacology 0 42157429

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