Affinage

SETD6

N-lysine methyltransferase SETD6 · UniProt Q8TBK2

Length
473 aa
Mass
53.2 kDa
Annotated
2026-04-28
29 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SETD6 is a protein lysine monomethyltransferase that modifies a broad spectrum of non-histone substrates—including RelA, PAK4, PLK1, BRD4, TWIST1, E2F1, WDR5, RAD18, and the histone variant H2AZ—to regulate NF-κB signaling, Wnt/β-catenin transcription, mitotic progression, DNA damage repair, chromatin state, and cell adhesion (PMID:21131967, PMID:26841865, PMID:30622182, PMID:34039605, PMID:35694846, PMID:40866490). Substrate specificity is governed by sequence context at positions −1, +2, and +3 relative to the target lysine, enabling SETD6 to act as a multispecific enzyme whose methylation events serve as molecular switches—for example, RelA K310 monomethylation recruits the GLP methyltransferase to silence NF-κB target genes, BRD4 K99 methylation controls E2F1 recruitment and mRNA translation, and E2F1 K117 methylation antagonizes acetylation-dependent BRD4 binding (PMID:41157251, PMID:21131967, PMID:34039605, PMID:41540805). SETD6 catalytic activity is itself regulated by SAM-dependent oligomerization and auto-methylation at K179, which promotes trimerization and increases catalytic rate (PMID:30189201). A truncating SETD6 mutation that abolishes methyltransferase activity while retaining substrate binding acts as a dominant negative and segregates with familial colorectal cancer type X (PMID:28973356).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2010 High

    The discovery that SETD6 monomethylates RelA at K310 established it as a non-histone protein lysine methyltransferase and revealed a methylation-phosphorylation switch governing NF-κB-dependent gene repression, answering how chromatin silencing at inflammatory genes is coupled to NF-κB post-translational modification.

    Evidence PKMT screen of >40 candidates, in vitro methylation, Co-IP, ChIP, and primary immune cell assays

    PMID:21131967

    Open questions at the time
    • Endogenous stoichiometry of RelA K310me1 in different cell types unknown
    • Whether SETD6 methylates additional NF-κB family members not tested
    • In vivo physiological role in inflammation not yet demonstrated
  2. 2011 High

    Solving the crystal structure of SETD6 bound to the RelA K310 peptide and SAM defined the structural basis for substrate recognition and explained how Ser311 phosphorylation sterically blocks both methylation and GLP ankyrin-repeat reading.

    Evidence X-ray crystallography, structural modeling, peptide binding assays

    PMID:21515635

    Open questions at the time
    • No structure with a non-RelA substrate available
    • Dynamic conformational changes upon SAM binding not resolved
    • Co-crystal with GLP ankyrin domain not obtained
  3. 2013 High

    Identification of H2AZ K7 as a SETD6 histone substrate expanded its repertoire beyond non-histone proteins and linked its activity to co-occupancy with H3K27me3 at developmental gene promoters, explaining how SETD6 contributes to embryonic stem cell self-renewal.

    Evidence In vitro methylation, mass spectrometry, ChIP, Setd6 knockdown in mESCs

    PMID:23324626

    Open questions at the time
    • Reader of H2AZK7me1 not identified
    • Whether H2AZK7me1 directly recruits PRC2 or acts independently unknown
    • Phenotype in Setd6-null mouse embryos not reported
  4. 2014 Medium

    The finding that SETD6 associates with ERα and acts as a co-activator of estrogen-responsive genes, despite interacting with repressive factors (HDAC1, MTA2), revealed a context-dependent transcriptional role and linked SETD6 to breast cancer cell proliferation and survival.

    Evidence Co-IP/mass spectrometry, luciferase reporter, siRNA knockdown, flow cytometry in breast carcinoma cells

    PMID:24751716

    Open questions at the time
    • Direct methylation substrate in the ERα pathway not identified
    • Mechanism by which SETD6 co-activates despite HDAC1/MTA2 association unclear
    • No in vivo breast cancer model tested
  5. 2016 High

    Demonstration that SETD6 methylates PAK4 to promote PAK4–β-catenin interaction and Wnt target gene activation, and separately that SETD6 negatively regulates Nrf2 signaling through a catalytically independent interaction with DJ1, established SETD6 as a signaling hub acting through both methyltransferase-dependent and -independent mechanisms.

    Evidence In vitro methylation, Co-IP, ChIP, Wnt and Nrf2 reporter assays, siRNA depletion

    PMID:26780326 PMID:26841865

    Open questions at the time
    • Specific PAK4 methylation site not yet mapped (resolved later)
    • DJ1 interaction interface not structurally defined
    • In vivo validation of Wnt and Nrf2 roles absent
  6. 2017 Medium

    A familial colorectal cancer type X-associated truncating mutation (p.Met264IlefsTer3) that abolishes catalytic activity while retaining substrate binding demonstrated a dominant-negative mechanism and provided genetic evidence linking SETD6 loss-of-function to cancer predisposition.

    Evidence Whole-exome sequencing, in vitro methylation, Co-IP, localization imaging

    PMID:28973356

    Open questions at the time
    • Only one family studied; penetrance and prevalence unknown
    • Whether dominant-negative effect occurs for all substrates not tested
    • Animal model recapitulating colorectal tumorigenesis not generated
  7. 2018 High

    Discovery that SETD6 auto-methylates at K179 to drive trimerization and catalytic activation, and that SAM stabilizes oligomeric states, revealed an intrinsic regulatory layer controlling enzyme output.

    Evidence SEC, SAXS, radioactive methylation, mass spectrometry, mutagenesis, kinetic analysis

    PMID:30189201

    Open questions at the time
    • Physiological relevance of oligomerization in cells not demonstrated
    • Whether auto-methylation is regulated by upstream signals unknown
    • No reader identified for SETD6 auto-methylation marks
  8. 2019 High

    SETD6 methylation of PLK1 at K209/K413 restrains PLK1 kinase activity and slows mitotic progression, placing SETD6 as a mitotic brake and extending its functional scope to cell division control.

    Evidence In vitro methylation, Co-IP, PLK1 kinase assay, time-lapse microscopy, SETD6 KO cells

    PMID:30622182

    Open questions at the time
    • How PLK1 methylation mechanistically dampens kinase activity not resolved
    • Consequences for chromosome segregation fidelity not assessed
    • Cell-cycle-dependent regulation of SETD6 itself not defined
  9. 2019 Medium

    In vivo knockdown of Setd6 in rat hippocampus impaired long-term memory consolidation and disrupted RelA K310me1-dependent chromatin silencing at neuronal genes, providing the first in vivo physiological role for SETD6 outside cancer.

    Evidence siRNA knockdown in vivo, Co-IP, ChIP, electrophysiology, behavioral memory tests, dendritic spine imaging

    PMID:31378303

    Open questions at the time
    • Specific neuronal target genes directly regulated by SETD6 methylation not comprehensively mapped
    • Contribution of substrates other than RelA to memory phenotype not dissected
    • Genetic knockout model not used
  10. 2020 High

    Mapping PAK4 K473 as the primary SETD6 methylation site and linking it to β-catenin activation, reduced focal adhesion assembly, and decreased migration refined the mechanism by which SETD6 connects Wnt signaling to cytoskeletal remodeling.

    Evidence In vitro methylation, mutagenesis, β-catenin reporter, focal adhesion imaging, migration/invasion assays

    PMID:33051544

    Open questions at the time
    • Reader that recognizes PAK4-K473me1 not identified
    • Whether K473 methylation affects PAK4 kinase activity directly not tested
    • In vivo relevance in tumor models not established
  11. 2021 High

    SETD6 methylation of BRD4 at K99 was shown to control E2F1 recruitment to translation-related gene promoters and repress global mRNA translation, revealing a new axis by which a methyltransferase regulates translational output via chromatin-level control.

    Evidence In vitro methylation, ChIP-seq, RNA-seq, ribosome/polysome profiling, BRD4-K99R mutagenesis, Co-IP

    PMID:34039605

    Open questions at the time
    • Structural basis for how K99me1 alters E2F1 recruitment unknown
    • Whether BRD4 K99 methylation is dynamic and regulated by a demethylase not explored
    • Genome-wide methylation-dependent BRD4 redistribution only partially characterized
  12. 2022 High

    Methylation of TWIST1 at K33 by SETD6 was shown to recruit EZH2 and deposit H3K27me3 at the LINC-PINT locus, repressing this lncRNA and promoting EMT in glioma cells, thereby linking SETD6 to epigenetic silencing of a tumor-suppressive lncRNA.

    Evidence In vitro methylation, ChIP, RNA-seq, siRNA/KO, migration assays, mutagenesis

    PMID:35694846

    Open questions at the time
    • Whether TWIST1 K33me1 is a general EMT signal beyond LINC-PINT unknown
    • Reader that bridges TWIST1 K33me1 to EZH2 not identified
    • In vivo glioma model not tested
  13. 2023 Medium

    Identification of a SETD6–E2F1 positive feedback loop—where E2F1 activates SETD6 transcription and SETD6 methylates E2F1 at K117 to further enhance its own expression—revealed a self-reinforcing mechanism for maintaining SETD6 levels.

    Evidence In vitro methylation, ChIP, promoter-luciferase reporter, qRT-PCR, mutagenesis, siRNA

    PMID:37690684

    Open questions at the time
    • How the feedback loop is broken or modulated in normal cells not defined
    • Genome-wide consequences of the loop not assessed
    • Interplay with E2F1 K117 acetylation not yet explored (resolved later)
  14. 2025 Medium

    Systematic peptide array scanning and AlphaFold3 docking defined the substrate-recognition grammar of SETD6—positions −1, +2, and +3 relative to the target lysine—and mutagenesis of SETD6 L260 confirmed substrate-specific recognition differences, explaining how one enzyme achieves multispecificity.

    Evidence Peptide SPOT array methylation, AlphaFold3 docking, L260 mutagenesis

    PMID:41157251

    Open questions at the time
    • Full quantitative kinetic parameters for each substrate in the defined grammar not reported
    • Predictions for novel substrates not experimentally validated
    • Structural validation by co-crystallography with non-RelA substrates lacking
  15. 2025 High

    SETD6 methylation of RAD18 at K73/K406 influences RAD18 nuclear localization and is required for attenuating DNA breaks, linking SETD6 catalytic activity to the DNA damage response.

    Evidence Protein microarray, mass spectrometry, Co-IP, mutagenesis, γH2AX blot, comet assay, catalytic-dead rescue

    PMID:40866490

    Open questions at the time
    • Whether RAD18 methylation affects PCNA ubiquitination or translesion synthesis not tested
    • Specific DNA repair pathway engaged by methylated RAD18 not delineated
    • In vivo genomic instability phenotype not assessed
  16. 2026 High

    Defining a methyl–acetyl switch on E2F1 K117—where SETD6-mediated methylation blocks acetylation and BRD4 bromodomain binding—established a binary regulatory logic controlling E2F1 chromatin binding and distinct oncogenic gene programs in prostate cancer.

    Evidence In vitro methylation/acetylation, ChIP-seq, RNA-seq, Co-IP, mutagenesis, bromodomain binding assay

    PMID:41540805

    Open questions at the time
    • Acetyltransferase responsible for E2F1 K117 acetylation not identified
    • Whether the switch operates in non-cancer contexts unknown
    • Demethylase that could reverse K117me1 not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of demethylases that reverse SETD6-deposited marks, the structural basis for substrate recognition beyond RelA, the in vivo physiological consequences of SETD6 loss in genetic animal models, and whether SETD6 auto-methylation-dependent oligomerization is regulated in cells.
  • No SETD6-specific demethylase identified for any substrate
  • No conditional knockout mouse phenotype reported
  • In vivo relevance of auto-methylation-driven oligomerization untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 13
Localization
GO:0005694 chromosome 5 GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 1
Partners
BRD4E2F1PAK4PLK1RAD18RELATWIST1WDR5

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 SETD6 monomethylates the NF-κB subunit RelA at Lys310 (RelAK310me1), rendering RelA transcriptionally inert. RelAK310me1 is recognized by the ankyrin repeat of GLP, which promotes H3K9 methylation and a repressed chromatin state at RelA target genes. PKC-ζ-mediated phosphorylation of RelA at Ser311 blocks GLP binding to RelAK310me1, relieving repression upon NF-κB activation. PKMT screen (>40 candidates), in vitro methylation assays, Co-IP, chromatin immunoprecipitation, primary immune cell inflammatory assays Nature immunology High 21131967
2011 Crystal structure of SETD6 in complex with the RelA peptide containing K310 and S-adenosyl-L-methionine reveals a V-like protein structure; structural modeling shows Ser311 phosphorylation sterically inhibits both K310 methylation by SETD6 and binding of K310me1 by GLP ankyrin repeats; SETD6 is structurally similar to Rubisco large subunit methyltransferase. X-ray crystallography, structural modeling, peptide binding assays Nucleic acids research High 21515635
2013 SETD6 monomethylates the histone H2A variant H2AZ at lysine 7 (H2AZK7me1). In mouse embryonic stem cells, H2AZK7me1 and H3K27me3 co-occupy transcriptional start sites of differentiation genes; depletion of Setd6 causes mESC differentiation and impairs self-renewal. In vitro methylation assay, mass spectrometry, ChIP, Setd6 knockdown in mESCs Epigenetics High 23324626
2014 SETD6 associates with estrogen receptor α (ERα), HDAC1, MTA2, and TRRAP. Despite associating with repressive factors, SETD6 acts as a co-activator of estrogen-responsive genes (PGR, TFF1); silencing SETD6 induces proliferation defects, upregulates CDKN1A, and triggers apoptosis in breast carcinoma cells. Co-IP/mass spectrometry, luciferase reporter assay, siRNA knockdown, flow cytometry Epigenetics Medium 24751716
2016 SETD6 methylates PAK4 both in vitro and at chromatin in cells; SETD6-mediated PAK4 methylation promotes physical interaction between PAK4 and β-catenin, leading to increased transcription of Wnt/β-catenin target genes. Depletion of SETD6 significantly hinders activation of Wnt/β-catenin target genes. In vitro methylation assay, Co-IP, ChIP, siRNA depletion, Wnt reporter assay The Journal of biological chemistry High 26841865
2016 SETD6 acts as a negative regulator of the Nrf2-mediated oxidative stress response through a direct, catalytically independent interaction with DJ1 at chromatin. SETD6 binds DJ1 in vitro and in cells but does not methylate it; under basal conditions this interaction inhibits DJ1 activity and represses Nrf2 target gene transcription. Upon oxidative stress, SETD6 levels decrease, weakening the SETD6-DJ1 interaction and allowing Nrf2 target gene induction. In vitro binding assay, Co-IP, ChIP, siRNA depletion, qRT-PCR of Nrf2 target genes Biochimica et biophysica acta Medium 26780326
2017 A truncating mutation in SETD6 (p.Met264IlefsTer3) found in familial colorectal cancer type X abolishes methyltransferase activity while retaining expression, subcellular localization, and substrate-binding ability; the truncated protein acts as a dominant negative by competing with wild-type SETD6 for substrates. Whole-exome sequencing, in vitro methylation assay, Co-IP, localization imaging Human molecular genetics Medium 28973356
2017 A 15-amino acid cell-penetrating peptide derived from RelA residues 302-316 (containing K310) directly and specifically inhibits SETD6 methyltransferase activity in vitro and in cells, demonstrating that the RelA substrate sequence is sufficient for competitive inhibition of SETD6 catalysis. In vitro methylation inhibition assay, cell treatment with CPP-fused peptide, functional cell migration/proliferation readout Oncotarget Medium 29435148
2018 SETD6 forms high-molecular-weight oligomers (monomers, dimers, trimers) stabilized by SAM. SETD6 auto-methylates itself at K39, K179, and K372; auto-methylation at K179 (in the SET domain) is required for trimer formation, and auto-methylation at K39 and K179 increases SETD6 catalytic rate in vitro. SEC, SAXS, radioactive in vitro methylation, mass spectrometry, site-directed mutagenesis, kinetic analysis Journal of molecular biology High 30189201
2018 SETD6 monomethylates WDR5 at lysines K207 and K325; disrupting these methylation sites via K207R/K325R double mutation attenuates WDR5-promoted breast cancer cell proliferation and migration and partially reduces global H3K4me3 levels without affecting MLL/SET1 complex assembly. In vitro methylation assay, site-directed mutagenesis, cell proliferation/migration assays, western blot for H3K4me3 Oncology reports Medium 30226578
2019 SETD6 binds and methylates PLK1 at K209 and K413 during mitosis. SETD6-deficient cells and cells expressing non-methylatable PLK1 (K209R/K413R) show increased PLK1 kinase activity, accelerated mitotic progression, and faster cellular proliferation, placing SETD6 as a brake on mitotic pace through PLK1 methylation. In vitro methylation assay, Co-IP, PLK1 kinase activity assay, time-lapse microscopy, SETD6 KO cell analysis Proceedings of the National Academy of Sciences of the United States of America High 30622182
2019 SETD6 is required for memory consolidation in the rat dorsal hippocampus; siRNA-mediated knockdown of Setd6 reduces RelA K310 monomethylation and associated H3K9me2 in hippocampal neurons, impairs spine morphology, disrupts gene expression, and blocks long-term memory formation. siRNA knockdown in vivo, Co-IP, ChIP, electrophysiology, behavioral memory tests, dendritic spine imaging Biological psychiatry Medium 31378303
2020 SETD6 methylates PAK4 at K473 as its primary methylation site; methylation at K473 activates β-catenin transcriptional activity, inhibits cell adhesion, attenuates paxillin localization to focal adhesions, reduces filopodia and actin structures, and decreases cell migration and invasion. In vitro methylation assay, site-directed mutagenesis, β-catenin reporter assay, immunofluorescence/focal adhesion imaging, migration and invasion assays Scientific reports High 33051544
2021 SETD6 methylates BRD4 at K99 on chromatin; BRD4 K99 methylation negatively regulates expression of genes involved in mRNA translation and inhibits total mRNA translation in cells. Mechanistically, K99 methylation does not affect BRD4 association with acetylated histone H4 but determines specific recruitment of transcription factor E2F1 to translation-related target genes. In vitro methylation assay, ChIP-seq, RNA-seq, ribosome profiling/polysome profiling, BRD4-K99R mutagenesis, Co-IP Science advances High 34039605
2022 SETD6 methylates TWIST1 at K33 at chromatin; K33 methylation of TWIST1 increases EZH2 occupancy and H3K27me3 deposition at the LINC-PINT locus, repressing LINC-PINT lncRNA expression and thereby promoting EMT in glioma cells. Unmethylated TWIST1 dissociates from the locus, permitting LINC-PINT expression and increased cell adhesion. In vitro methylation assay, ChIP, RNA-seq, siRNA/KO, cell adhesion and migration assays, site-directed mutagenesis Nucleic acids research High 35694846
2022 SETD6 co-immunoprecipitates with BRD4/E2 protein complex and is detected at the HPV long control region enhancer by ChIP; SETD6 depletion reduces HPV-31 transcription in episomal cells; BRD4-K99R mutant shows decreased binding to HPV-31 E2, demonstrating that SETD6 methylation of BRD4 K99 facilitates E2-BRD4 interaction and HPV transcriptional activation. Co-IP, ChIP, siRNA knockdown, luciferase reporter assay, BRD4-K99R mutagenesis Journal of virology Medium 36300937
2022 SETD6 and SETD3 share 52 interacting proteins enriched for transcription regulators and ~100 commonly regulated genes; double KO of SETD6 and SETD3 in HeLa cells produces elevated apoptosis not seen with single KOs, indicating a synthetic-lethal relationship and a joint role in suppressing apoptosis. Co-IP/mass spectrometry proteomics, RNA-seq of single and double KO cells, flow cytometry apoptosis assay Biochimie Medium 35550916
2023 SETD6 monomethylates transcription factor E2F1 at K117 in vitro and in cells; E2F1 binds the SETD6 promoter and activates SETD6 mRNA expression; E2F1 K117 methylation by SETD6 further enhances SETD6 expression, establishing a positive feedback loop. E2F1-K117R (non-methylatable) mutant or SETD6 depletion reverses this upregulation. In vitro methylation assay, ChIP, promoter-luciferase reporter, qRT-PCR, site-directed mutagenesis, siRNA knockdown The Journal of biological chemistry Medium 37690684
2025 SETD6 binds and methylates RAD18 at K73 and K406 (identified by mass spectrometry and site-directed mutagenesis); RAD18 methylation influences its nuclear localization—SETD6 KO cells show increased nuclear RAD18. SETD6 depletion elevates γH2AX levels and DNA breaks (comet assay); restoring wild-type but not catalytically inactive SETD6 reduces DNA damage, indicating SETD6 enzymatic activity is required for attenuating DNA breaks via RAD18 methylation. Protein microarray, ELISA, Co-IP, mass spectrometry, site-directed mutagenesis, immunofluorescence (localization), γH2AX western blot, comet assay Scientific reports High 40866490
2025 Peptide SPOT array and AlphaFold3 docking reveal that SETD6 reads substrate sequences at positions -1, +2, and +3 relative to the target lysine (favoring Gly or large aliphatic at -1, Ile/Val at +2, Lys at +3), and that these preferences are substrate-context-dependent; mutation of SETD6 residue L260 (which contacts the +2 position in the SETD6-RELA crystal structure) confirms substrate-specific differences in recognition, explaining SETD6 multispecificity. Peptide SPOT array methylation assay, AlphaFold3 structural docking, site-directed mutagenesis of SETD6 L260 Life (Basel, Switzerland) Medium 41157251
2025 In melanoma cells, SETD6 methylates BRD4 at K99; SETD6 KO or BRD4-K99R mutation disrupts BRD4 genomic occupancy. SETD6 also interacts with melanoma master transcription factor MITF; BRD4 and MITF form a chromatin-localized complex whose assembly depends on both SETD6-mediated BRD4 methylation and MITF acetylation, and this complex controls selective BRD4 and MITF genomic localization. ChIP-seq, Co-IP, SETD6 KO, BRD4-K99R mutagenesis, immunoprecipitation NAR cancer Medium 40809945
2026 SETD6 monomethylates E2F1 at K117; K117 methylation prevents K117 acetylation and thereby blocks BRD4 bromodomain binding to E2F1. This methylation/acetylation switch on E2F1-K117 alters E2F1 chromatin binding and controls distinct sets of target genes, influencing oncogenic phenotypes in prostate cancer cells. In vitro methylation and acetylation assays, ChIP-seq, RNA-seq, Co-IP, site-directed mutagenesis, biochemical bromodomain binding assay Nucleic acids research High 41540805
2024 SETD6 binds and methylates Aurora-B kinase at two adjacent lysine residues; upon replication stress, Aurora-B methylation by SETD6 increases. SETD6-depleted HeLa cells show chromatin bridges, actin patches, multinucleation, and reduced Aurora-B kinase activity during cytokinesis, placing SETD6-mediated Aurora-B methylation as a regulator of cytokinesis fidelity and chromosomal stability. Proteomic screen, in vitro methylation assay, SETD6 KO, live-cell imaging (chromatin bridges, actin patches), Aurora-B kinase activity assay, multinucleation quantification bioRxivpreprint Medium bio_10.1101_2024.12.22.629973

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling. Nature immunology 219 21131967
2011 Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling. Nucleic acids research 59 21515635
2013 SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal. Epigenetics 57 23324626
2016 PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/β-Catenin Pathway. The Journal of biological chemistry 56 26841865
2019 The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation. Proceedings of the National Academy of Sciences of the United States of America 34 30622182
2014 SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells. Epigenetics 31 24751716
2021 BRD4 methylation by the methyltransferase SETD6 regulates selective transcription to control mRNA translation. Science advances 28 34039605
2017 SETD6 regulates NF-κB signaling in urothelial cell survival: Implications for bladder cancer. Oncotarget 27 28122346
2017 SETD6 dominant negative mutation in familial colorectal cancer type X. Human molecular genetics 25 28973356
2016 SETD6 is a negative regulator of oxidative stress response. Biochimica et biophysica acta 24 26780326
2020 Down-regulation of SETD6 protects podocyte against high glucose and palmitic acid-induced apoptosis, and mitochondrial dysfunction via activating Nrf2-Keap1 signaling pathway in diabetic nephropathy. Journal of molecular histology 18 32803470
2019 MiR-411 inhibits gastric cancer proliferation and migration through targeting SETD6. European review for medical and pharmacological sciences 18 31081088
2020 PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion. Scientific reports 17 33051544
2022 TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in glioma. Nucleic acids research 16 35694846
2018 Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration. Oncology reports 14 30226578
2017 Peptide inhibition of the SETD6 methyltransferase catalytic activity. Oncotarget 13 29435148
2022 SETD6 Regulates E2-Dependent Human Papillomavirus Transcription. Journal of virology 9 36300937
2018 Oligomerization and Auto-methylation of the Human Lysine Methyltransferase SETD6. Journal of molecular biology 9 30189201
2023 Methylation of the transcription factor E2F1 by SETD6 regulates SETD6 expression via a positive feedback mechanism. The Journal of biological chemistry 8 37690684
2022 Structure-function conservation between the methyltransferases SETD3 and SETD6. Biochimie 6 35550916
2021 Silencing of SETD6 inhibits the tumorigenesis of oral squamous cell carcinoma by inhibiting methylation of PAK4 and RelA. Histology and histopathology 6 33710605
2019 The SETD6 Methyltransferase Plays an Essential Role in Hippocampus-Dependent Memory Formation. Biological psychiatry 6 31378303
2016 Proteomic analysis of SETD6 interacting proteins. Data in brief 5 26937450
2025 Orchestrating epigenetics: a comprehensive review of the methyltransferase SETD6. Experimental & molecular medicine 4 40102573
2023 Investigating the functional role of SETD6 in lung adenocarcinoma. BMC cancer 3 36604642
2025 RAD18 methylation by the methyltransferase SETD6 attenuates DNA breaks. Scientific reports 1 40866490
2025 Mechanisms of Substrate Recognition by the Multispecific Protein Lysine Methyltransferase SETD6. Life (Basel, Switzerland) 1 41157251
2026 E2F1 K117 methylation by SETD6 disrupts BRD4-E2F1 binding and modulates E2F1 chromatin binding and gene regulation in prostate cancer cells. Nucleic acids research 0 41540805
2025 SETD6 mediates selective interaction and genomic occupancy of BRD4 and MITF in melanoma cells. NAR cancer 0 40809945