Affinage

SETD1A

Histone-lysine N-methyltransferase SETD1A · UniProt O15047

Length
1707 aa
Mass
186.0 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SETD1A is the catalytic subunit of the human SET1/COMPASS complex, a major histone H3 lysine 4 (H3K4) methyltransferase that deposits mono-, di-, and trimethylation marks at active gene promoters and is essential for embryonic development, hematopoiesis, and stem cell maintenance (PMID:12670868, PMID:25561738, PMID:24550110). The complex is recruited to transcription start sites through Wdr82 binding to Ser5-phosphorylated RNA Pol II CTD, while additional targeting by HCF-1, CFP1/CXXC1, Nup98, Oct4, KLF4, AP-1, and HIF1α directs H3K4me3 deposition at specific promoters and enhancers to activate lineage-appropriate gene expression programs (PMID:17998332, PMID:19951360, PMID:29269482, PMID:26785054, PMID:25814673). Beyond canonical histone methylation, SETD1A methylates the non-histone substrate YAP at K342 to block its CRM1-dependent nuclear export (PMID:30008322), promotes FANCD2-dependent stalled replication fork protection through H3K4 methylation (PMID:29937342), facilitates RIF1-dependent NHEJ at DNA double-strand breaks (PMID:35439434), and possesses a non-catalytic FLOS domain that recruits cyclin K to chromatin for DNA-damage-response gene expression independently of SET domain activity (PMID:29474905). SETD1A haploinsufficiency in mouse and human neuronal models causes altered dendritic morphology, synaptic dysfunction, and working memory deficits rescued by LSD1 inhibition or cAMP pathway modulation, establishing SETD1A as a neurodevelopmental disease gene (PMID:31606247, PMID:35508131).

Mechanistic history

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

    Identification of SETD1A as the catalytic subunit of a human H3K4 methyltransferase complex tethered by HCF-1 established the first biochemical activity for this gene and linked it to transcriptional activation through histone modification.

    Evidence Co-immunoprecipitation and in vitro HMT assay on recombinant histones

    PMID:12670868

    Open questions at the time
    • Substrate specificity for mono- vs. di- vs. trimethylation not resolved
    • Distinction from MLL family complexes not yet established
  2. 2007 High

    Discovery that Wdr82 bridges SETD1A to Ser5-phosphorylated RNA Pol II CTD explained how the complex is co-transcriptionally recruited to transcription start sites, answering the targeting question.

    Evidence ChIP, Co-IP, and siRNA knockdown showing loss of SETD1A occupancy and H3K4me3 upon Wdr82 depletion

    PMID:17998332

    Open questions at the time
    • Whether Wdr82-CTD interaction is sufficient for all SETD1A genomic targeting unclear
    • Structural basis of Wdr82-CTD recognition not determined
  3. 2008 High

    Demonstration that Wdr82 is unique to SET1A/B complexes (not MLL1-4) and that SET1A is a more robust trimethylase than MLLs clarified the non-redundant catalytic role of SETD1A among COMPASS family members.

    Evidence Mass spectrometry, in vitro HMT assay, and RNAi knockdown

    PMID:18838538

    Open questions at the time
    • Genomic partitioning of H3K4me3 between SETD1A and SETD1B not resolved
    • Degree of in vivo redundancy among COMPASS members unknown
  4. 2009 High

    Finding that CFP1/CXXC1 restricts SETD1A to euchromatin revealed a DNA-binding-dependent targeting mechanism that prevents aberrant heterochromatic localization.

    Evidence CXXC1 knockout ESCs with immunofluorescence and structure-function analysis

    PMID:19951360

    Open questions at the time
    • Whether CFP1 CpG island recognition fully accounts for SETD1A promoter specificity unclear
    • CFP1-independent targeting mechanisms not characterized
  5. 2012 High

    Structural determination of WDR5 bound to the SET1A Win motif and demonstration that WDR5 is required for WRAD-stimulated methyltransferase activity defined the core regulatory architecture of the COMPASS complex.

    Evidence X-ray crystallography (1.2–1.9 Å) and in vitro enzymatic assays

    PMID:22266653 PMID:22665483

    Open questions at the time
    • Full complex structure of SET1A with all subunits not available
    • Allosteric mechanism of WRAD stimulation not fully elucidated
  6. 2013 High

    Discovery of TET2/3-OGT-mediated GlcNAcylation of HCF-1 as a requirement for COMPASS integrity and chromatin binding introduced a metabolic/epigenetic crosstalk layer regulating SETD1A recruitment.

    Evidence Co-IP, ChIP, siRNA, and Tet2 knockout mouse

    PMID:23353889

    Open questions at the time
    • Which specific GlcNAc sites on HCF-1 are critical not mapped
    • Whether this regulation applies equally to SETD1A and SETD1B unclear
  7. 2014 High

    Conditional knockout studies established SETD1A as essential for embryonic development from the epiblast stage and for maintaining bulk H3K4 methylation, pluripotency gene expression, and cell cycle progression in ESCs.

    Evidence Conditional KO mouse and ES cell deletion with flow cytometry and gene expression analysis

    PMID:24550110

    Open questions at the time
    • Relative contribution of catalytic vs. non-catalytic functions to ESC phenotype not separated
    • Whether SETD1B compensates in any tissues not addressed
  8. 2014 High

    Demonstration that Setd1a-dependent H3K4me3 at Pax5 and Rag1/2 loci is required for IgH enhancer–VH looping and B cell development defined a specific lineage-restricted role in long-range chromatin architecture.

    Evidence Conditional KO mouse with ChIP, 3C chromatin looping, and flow cytometry

    PMID:25550471

    Open questions at the time
    • Whether SETD1A directly mediates loop formation or acts through intermediary looping factors unknown
    • Contribution to other immunoglobulin rearrangements not examined
  9. 2015 High

    Full biochemical reconstitution showed SET1A alone catalyzes weak monomethylation, while WRAD addition stimulates monomethylation and confers di-/trimethylation, resolving the product specificity mechanism.

    Evidence In vitro reconstitution of purified SET1A core complex with WRAD subunits

    PMID:25561738

    Open questions at the time
    • How chromatin context modulates product specificity in vivo not tested
    • Role of non-core subunits (CFP1, Wdr82) in product regulation not examined in reconstituted system
  10. 2016 High

    Identification of Oct4 as a direct, Wdr5-independent interactor of SETD1A that recruits it to pluripotency gene promoters explained how SETD1A is targeted to stem-cell-specific loci beyond the general Pol II CTD mechanism.

    Evidence Co-IP, ChIP-seq, KO mouse, ESC maintenance and iPSC reprogramming assays

    PMID:26785054

    Open questions at the time
    • Whether other pluripotency factors recruit SETD1A through similar mechanisms unknown
    • Structural basis of Oct4-SETD1A interaction not determined
  11. 2016 Medium

    Multiple studies showed SETD1A is recruited by diverse transcription factors (AP-1, KLF4, ERα, HIF1α) to specific promoters and enhancers, establishing a general model of transcription-factor-directed SETD1A targeting for context-dependent gene activation.

    Evidence ChIP, Co-IP, siRNA, and conditional KO in endothelial, erythroid, and cancer cell systems

    PMID:25814673 PMID:27141965 PMID:30191958 PMID:32291851

    Open questions at the time
    • Whether SETD1A directly contacts all reported TFs or acts through bridging factors not always confirmed
    • Relative quantitative contributions of different recruiting TFs at shared loci not measured
  12. 2017 High

    Separation of catalytic and non-catalytic functions showed the SET domain is dispensable for ESC self-renewal but required for differentiation, establishing that SETD1A operates as both an enzyme and a scaffolding platform.

    Evidence CRISPR SET domain deletion in ESCs with ChIP-seq and differentiation assays

    PMID:28939616

    Open questions at the time
    • Molecular identity of non-catalytic function (later identified as FLOS/cyclin K) not resolved in this study
    • Which differentiation-specific genes require catalytic activity not fully catalogued
  13. 2017 High

    Discovery that Nup98 recruits SETD1A/COMPASS to transcription start sites in hematopoietic cells identified a nuclear-pore-associated targeting pathway, expanding the repertoire of SETD1A recruitment mechanisms.

    Evidence ChIP-seq, Co-IP, and siRNA/shRNA depletion in hematopoietic cells

    PMID:29269482

    Open questions at the time
    • Whether Nup98 acts at the nuclear pore or as a mobile nucleoplasmic factor unclear
    • Relationship to Nup98-fusion oncoproteins in leukemia not mechanistically resolved
  14. 2018 High

    Identification of a non-catalytic FLOS domain in SETD1A that binds cyclin K and recruits it to chromatin for S-phase DNA damage response gene expression resolved the molecular basis of SETD1A's SET-domain-independent survival function in AML cells.

    Evidence CRISPR domain screen, mutagenesis, Co-IP, ChIP, and gene expression analysis

    PMID:29474905

    Open questions at the time
    • Whether FLOS-cyclin K interaction is regulated by DNA damage signaling unknown
    • Structural basis of FLOS-cyclin K interaction not determined
  15. 2018 High

    Demonstration that SETD1A methylates H3K4 at stalled replication forks to enhance FANCD2-dependent RAD51 stabilization established a direct replication fork protection function beyond transcription.

    Evidence siRNA, in vitro methylation, DNA fiber assay, and FANCD2 chaperone-defective mutant

    PMID:29937342

    Open questions at the time
    • How SETD1A is recruited specifically to stalled forks not resolved
    • Whether other COMPASS members contribute to fork protection unknown
  16. 2018 High

    Discovery that SETD1A methylates the non-histone substrate YAP at K342, blocking CRM1-dependent nuclear export and promoting tumorigenesis, expanded SETD1A's substrate repertoire beyond histones.

    Evidence In vitro methylation assay, Co-IP, YAP K342 methylation knock-in mouse, colorectal tumorigenesis model

    PMID:30008322

    Open questions at the time
    • Whether additional non-histone substrates exist not systematically explored
    • Regulation of SET1A's selectivity for YAP vs. histones unknown
  17. 2019 High

    In vivo evidence that Setd1a haploinsufficiency causes cortical synaptic and working memory deficits rescuable by LSD1 inhibition established SETD1A as a neurodevelopmental disease gene and identified a druggable counteracting enzyme.

    Evidence Setd1a+/− mouse model with ChIP-seq, behavioral assays, and pharmacological rescue

    PMID:31606247

    Open questions at the time
    • Whether LSD1 inhibition acts on the same genomic loci as SETD1A not proven
    • Human genetic validation for schizophrenia risk not directly shown in this study
  18. 2022 High

    Identification of RIF1 as a reader of SETD1A-deposited H3K4me at DNA double-strand breaks that suppresses end resection and promotes NHEJ connected SETD1A to a second DNA repair pathway beyond replication fork protection.

    Evidence Direct binding assays, genetic depletion, telomere end-joining and class switch recombination assays, patient cells

    PMID:35439434

    Open questions at the time
    • Whether H3K4me at DSBs is a general feature or restricted to specific break types not resolved
    • Interplay between SETD1A-dependent NHEJ and its replication fork protection role not examined
  19. 2022 High

    Human iPSC-derived neuronal models of SETD1A haploinsufficiency revealed hyperactivation of the cAMP/PKA pathway as a molecular mechanism underlying increased dendritic complexity and network bursting, with pharmacological rescue validating this pathway.

    Evidence CRISPR SETD1A+/− iPSCs, multi-electrode array, RNA-seq, pharmacological cAMP pathway modulation

    PMID:35508131

    Open questions at the time
    • How H3K4me3 loss leads to cAMP/PKA hyperactivation not mechanistically elucidated
    • Whether cAMP pathway findings translate to in vivo models or patients unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full non-histone substrate repertoire of SETD1A, the structural basis of FLOS domain–cyclin K interaction, how SETD1A is specifically recruited to DNA damage sites versus transcription start sites, and whether the catalytic and scaffolding functions can be therapeutically targeted independently.
  • No systematic non-histone substrate screen reported
  • No cryo-EM or crystal structure of full-length SETD1A complex available
  • Mechanism switching between transcriptional and DNA repair roles uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 1 R-HSA-69306 DNA Replication 1
Partners
ASH2LCCNKCFP1HCF1NUP98RBBP5WDR5WDR82
Complex memberships
SET1/COMPASS (SET1A complex)WRAD (WDR5-RbBP5-ASH2L-DPY30)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Human SETD1A (Set1/Ash2 complex) methylates histone H3 at Lys4 (H3K4) but not if the neighboring K9 residue is already methylated; HCF-1 tethers this Set1/Ash2 HMT complex together with the Sin3 HDAC complex, and the VP16 transcriptional activator selectively binds HCF-1 associated with the Set1/Ash2 HMT complex in the absence of Sin3. Co-immunoprecipitation, in vitro histone methyltransferase assay, functional binding studies Genes & development High 12670868
2007 The Wdr82 component of the human SETD1A complex interacts with the RNA recognition motif of SETD1A and binds the Ser5-phosphorylated CTD of RNA polymerase II (but not unphosphorylated or Ser2-phosphorylated CTD), thereby recruiting SETD1A to transcription start sites of expressed genes and promoting H3K4 trimethylation at those sites. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown with H3K4me3 and SETD1A occupancy readout Molecular and cellular biology High 17998332
2013 TET2 and TET3 promote OGT activity, which GlcNAcylates HCF1, a component of the SET1/COMPASS complex; this modification is important for COMPASS integrity and promotes SETD1A binding to chromatin and H3K4me3 at active promoters. Co-immunoprecipitation, ChIP, siRNA knockdown, Tet2 knockout mouse model The EMBO journal High 23353889
2008 Wdr82 is a specific component of human SET1A/COMPASS but not MLL1-4 complexes; RNAi knockdown of Wdr82 reduces H3K4 trimethylation levels; in vitro enzymatic studies show the SET1A complex is a more robust H3K4 trimethylase than MLL complexes. In vitro histone methyltransferase assay, mass spectrometry, RNAi knockdown Molecular and cellular biology High 18838538
2013 Quantitative mass spectrometry of human SET1/MLL complexes identified Bod1 as a discriminator between SET1B and SET1A complexes, and determined stoichiometry of shared and unique subunits across all six COMPASS-like complexes. Label-free quantitative mass spectrometry, absolute protein quantification Molecular and cellular biology High 23508102
2012 WDR5 binds the Win motifs of SET1A and SET1B via a peptidyl-arginine-binding cleft, and this interaction is required for optimal stimulation of SET1A methyltransferase activity by the RbBP5-ASH2L heterodimer. Crystal structure determination (1.2–1.9 Å resolution), in vitro enzymatic assay, co-immunoprecipitation The Journal of biological chemistry High 22665483
2012 WDR5 binds the Win motifs of SET1A and SET1B through a plastic peptide-binding cleft, and biochemical assays confirm WDR5 plays an important role in stimulating SET1A and SET1B methyltransferase activity by RbBP5-ASH2L. Crystal structure, biochemical binding assay, enzymatic activity assay Nucleic acids research High 22266653
2015 Biochemical reconstitution of human SET1A core complex with WRAD showed that in the absence of WRAD SET1A catalyzes weak H3K4 monomethylation; addition of WRAD stimulates monomethylation and confers di- and trimethylation activity; SET1A activity differs from MLL family members in a manner correlated with evolutionary lineage. In vitro biochemical reconstitution of human SET1 family core complexes, enzymatic activity assay, phylogenetic scanning mutagenesis The Journal of biological chemistry High 25561738
2018 SETD1A methylates H3K4 at replication forks under replication stress; this H3K4 methylation enhances FANCD2-dependent histone chaperone activity, which stabilizes RAD51 nucleofilaments and prevents DNA2-dependent resection of stalled replication forks. siRNA depletion, in vitro H3K4 methylation assay, replication fork protection assay (nascent strand degradation by DNA fiber), co-immunoprecipitation, FANCD2 chaperone-defective mutant Molecular cell High 29937342
2018 SETD1A contains a non-catalytic 'FLOS' domain that binds cyclin K; this FLOS domain is required for chromosomal recruitment of cyclin K and for DNA-damage-response-associated gene expression in S phase, enabling survival of AML cells independently of the enzymatic SET domain. CRISPR-Cas9 domain screening, mutagenesis, co-immunoprecipitation, ChIP, gene expression analysis Cell High 29474905
2018 SET1A mediates mono-methylation of YAP at K342, which disrupts the binding of YAP to the nuclear export receptor CRM1, thereby blocking YAP nuclear export and promoting nuclear accumulation and tumorigenesis. In vitro methylation assay, co-immunoprecipitation, YAP K342 methylation knock-in mouse model, colorectal tumorigenesis assay Cancer cell High 30008322
2009 CXXC finger protein 1 (CFP1/CXXC1) is a component of the SETD1A complex that restricts SETD1A and H3K4me3 to euchromatin; loss of CFP1 causes subnuclear mislocalization of SETD1A into heterochromatin and decreased SETD1A protein levels; both CFP1 DNA-binding activity and its interaction with SETD1A are required for proper genomic targeting. Knockout ES cells (CXXC1−/−), immunofluorescence localization, structure-function analysis of CFP1 fragments The FEBS journal High 19951360
2017 Nup98 binds transcription start sites in hematopoietic cells and recruits the Wdr82-SETD1A/COMPASS complex; depletion of Nup98 or Wdr82 abolishes SETD1A recruitment to chromatin and eliminates H3K4me3 at adjacent promoters. ChIP-seq, ChIP, siRNA/shRNA depletion, co-immunoprecipitation Genes & development High 29269482
2014 Mouse Setd1a is required for embryonic development beginning at the epiblast stage; conditional deletion in embryonic stem cells causes rapid loss of bulk H3K4 methylation, loss of pluripotency gene expression, proliferation defects with G1 accumulation, and inability to reprogram neural stem cells. Conditional knockout mouse, ES cell deletion, flow cytometry, gene expression analysis Development (Cambridge, England) High 24550110
2017 The SET domain of SET1A is dispensable for ESC proliferation and self-renewal but is required for ESC differentiation; loss of the SET domain reduces H3K4me3 at only a subset of loci, indicating SET1A has both catalytic and non-catalytic functions during ESC biology; SET1A (not MLL2) acts as the H3K4 methylase on bivalent genes during differentiation. CRISPR-Cas9 SET domain deletion in ESCs, ChIP-seq, gene expression profiling, differentiation assay Genes & development High 28939616
2007 HCF-1 is required for recruitment of Set1 (SETD1A) and MLL1 to herpesvirus immediate early promoters, leading to H3K4 trimethylation and transcriptional activation during viral lytic infection. Chromatin immunoprecipitation, minimal promoter reporter assay, siRNA knockdown Proceedings of the National Academy of Sciences of the United States of America Medium 17578910
2019 In Setd1a+/− mice, Setd1a binds both promoters and enhancers with strong overlap with Mef2 on enhancers; Setd1a heterozygosity causes altered axonal branching, cortical synaptic dynamics, and working memory deficits; LSD1 is a major counteracting demethylase for Setd1a, and pharmacological LSD1 antagonism rescues behavioral and morphological deficits. ChIP-seq, heterozygous mouse model, behavioral assays, pharmacological rescue with LSD1 inhibitor Neuron High 31606247
2022 SETD1A (with BOD1L) methylates H3K4 at DNA double-strand breaks, which recruits RIF1 through direct binding of RIF1 to methylated H3K4; this facilitates NHEJ by suppressing nucleolytic end resection; loss of SETD1A impairs RIF1 localization to DSBs and compromises end-joining of dysfunctional telomeres and class switch recombination. Co-immunoprecipitation, direct binding assay (RIF1 binds H3K4me), genetic depletion, telomere end-joining assay, class switch recombination assay, patient-derived cell lines Molecular cell High 35439434
2016 SET1A is recruited to the endothelin-1 (ET-1) promoter by the transcription factor AP-1 (c-Jun/c-Fos) in response to angiotensin II; SET1A synergizes with AP-1 to activate ET-1 transcription by depositing H3K4me3 at the promoter, and endothelial-specific SET1A depletion in mice attenuates Ang II-induced cardiac hypertrophy. ChIP, co-immunoprecipitation, siRNA knockdown, conditional endothelial KO mouse, luciferase reporter assay Arteriosclerosis, thrombosis, and vascular biology Medium 25814673
2016 SET1A specifically interacts with Oct4 (but not Sox2, Klf4, or Myc) independently of Wdr5; SET1A is recruited by Oct4 to Oct4 target gene promoters to catalyze H3K4 methylation and activate transcription; SET1A is required for ESC maintenance and iPSC generation, and for generation of Oct4-positive inner cell mass in vivo. Co-immunoprecipitation, ChIP-seq, gene expression profiling, knockout mouse, ESC maintenance assay Stem cells (Dayton, Ohio) High 26785054
2018 SETD1A in hematopoietic stem cells is required for expression of DNA damage recognition and repair pathways; SETD1A-deficient LT-HSCs lose transcriptional identity, proliferative capacity, and stem cell function under replicative stress and inflammatory stimulation in vivo. Conditional knockout mouse (Setd1a deleted in LT-HSCs), transplantation assay, gene expression analysis, inflammatory challenge Blood High 29348130
2016 SETD1A and NURF complexes bind erythroid gene promoters and coordinately regulate H3K4me3, chromatin accessibility, and enhancer-promoter looping during erythroid differentiation; erythroid-specific Setd1a deletion in mice leads to reduced erythroblasts, peripheral blood RBCs, and hemoglobin levels. Conditional knockout mouse (erythroid compartment), ChIP-seq, ATAC-seq, 3C/chromatin looping assay, gene expression analysis Nucleic acids research High 27141965
2020 SETD1A interacts with HIF1α and is co-recruited with HIF1α to glycolytic gene promoters (HK2, PFK2); SETD1A catalyzes H3K4 methylation at these promoters to enhance HIF1α-dependent transcription of glycolytic genes and promote gastric cancer progression. Co-immunoprecipitation, ChIP, siRNA knockdown, glucose uptake and lactate assays, gene expression analysis Molecular oncology Medium 32291851
2018 Uhrf1 forms a complex with SETD1A/COMPASS and is required to maintain bivalent histone marks (H3K4me3/H3K27me3) at neuroectoderm and mesoderm specification genes in embryonic stem cells. Co-immunoprecipitation, ChIP-seq, Uhrf1 KO ESCs Nature communications Medium 29968706
2022 SETD1A haploinsufficiency in human iPSC-derived neuronal networks increases dendritic complexity and network bursting activity, with transcriptomic changes in glutamatergic synaptic function; the molecular basis involves hyperactivation of the cAMP/PKA pathway, and pharmacological cAMP pathway targeting rescues network deficits. CRISPR-Cas9 SETD1A+/− iPSC-derived neurons, multi-electrode array recording, RNA-seq, pharmacological rescue Cell reports High 35508131
2014 Setd1a deficiency in the hematopoietic compartment blocks progenitor B-cell-to-precursor B-cell development by reducing H3K4me3 at Pax5 and Rag1/2 loci, compromising long-range looped interactions of the IgH enhancer Eμ with VH genes and regulatory regions required for IgH rearrangement. Conditional knockout mouse, ChIP, 3C/chromatin looping assay, flow cytometry, gene expression analysis FASEB journal High 25550471
2016 SETD1A is involved in H3K4 methylation and recruitment of ERα to enhancer regions of ERα target genes, and is required for accessible chromatin structure at those enhancers; SETD1A depletion reduces cell proliferation, migration, and induces apoptosis in ER-positive breast cancer cells. siRNA knockdown, ChIP, ATAC-seq (chromatin accessibility), cell proliferation and migration assays International journal of cancer Medium 30191958
2021 SETD1A interacts with and stabilizes β-catenin (independent of the SET domain), and activates NEAT1 and EZH2 transcription via H3K4me3 enrichment at their promoters, forming a positive feedback loop with the Wnt/β-catenin pathway in NSCLC cells. Co-immunoprecipitation, ChIP, luciferase reporter assay, domain mutagenesis (SET domain deletion), siRNA knockdown Journal of experimental & clinical cancer research Medium 34645486
2011 SET-1A (SETD1A) is recruited to iNOS and COX-2 promoters in response to IL-1β in human osteoarthritic chondrocytes, catalyzing H3K4 di- and trimethylation; SET-1A silencing prevents IL-1-induced H3K4 methylation and iNOS/COX-2 expression. ChIP, siRNA knockdown, RT-PCR, Western blot Arthritis and rheumatism Medium 20862685
2018 The enzymes LSD1 (demethylase) and Set1A (H3K4 methyltransferase) are co-recruited with HBx to hepatitis B virus cccDNA promoters; Set1A expression correlates with cccDNA H3K4 methylation, and this correlates with active viral gene expression. ChIP, co-immunoprecipitation, siRNA knockdown Scientific reports Medium 27174370
2018 SETD1A is recruited to the THBD (thrombomodulin) promoter by the transcription factor KLF4; SETD1A mediates H3K4 trimethylation at this promoter to activate TM transcription in response to retinoic acid; additionally, SETD1A is recruited to the KLF4 promoter by RAR, creating a feed-forward mechanism. ChIP, co-immunoprecipitation, siRNA knockdown, gene expression analysis Biochimica et biophysica acta. Gene regulatory mechanisms Medium 29940355

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Molecular cell 889 12667453
2001 The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. The EMBO journal 502 11742990
2013 TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. The EMBO journal 409 23353889
2003 Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes & development 337 12670868
2016 Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nature neuroscience 331 26974950
2009 Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions. Cell 264 19379692
2008 Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS. Molecular and cellular biology 257 18838538
1997 SET1, a yeast member of the trithorax family, functions in transcriptional silencing and diverse cellular processes. Molecular biology of the cell 216 9398665
2005 Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Molecular cell 198 16039595
2013 Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes. Molecular and cellular biology 179 23508102
2002 Evidence that Set1, a factor required for methylation of histone H3, regulates rDNA silencing in S. cerevisiae by a Sir2-independent mechanism. Current biology : CB 176 11818070
2007 Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes. Molecular and cellular biology 174 17998332
2012 Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes. Molecular cell 154 23246437
2014 The H3K4 methyltransferase Setd1a is first required at the epiblast stage, whereas Setd1b becomes essential after gastrulation. Development (Cambridge, England) 151 24550110
2018 SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis. Cancer cell 146 30008322
2014 Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Neuron 144 24853937
2006 Protein interactions within the Set1 complex and their roles in the regulation of histone 3 lysine 4 methylation. The Journal of biological chemistry 129 16921172
2005 The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation. Cell 125 16143104
2013 The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation. Molecular cell 113 23453808
2016 Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory. eLife 112 27336723
2007 The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection. Proceedings of the National Academy of Sciences of the United States of America 112 17578910
2012 WRAD: enabler of the SET1-family of H3K4 methyltransferases. Briefings in functional genomics 107 22652693
2012 Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases. The Journal of biological chemistry 105 22665483
2012 The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases. Nucleic acids research 103 22266653
2007 Genome-wide, as opposed to local, antisilencing is mediated redundantly by the euchromatic factors Set1 and H2A.Z. Proceedings of the National Academy of Sciences of the United States of America 103 17925448
2002 Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast. Proceedings of the National Academy of Sciences of the United States of America 102 12193658
2019 Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice. Neuron 94 31606247
2006 Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1. Journal of virology 94 16731913
2018 Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2. Molecular cell 93 29937342
2015 Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation. The Journal of biological chemistry 92 25561738
2018 A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response. Cell 90 29474905
2005 Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae. The Journal of biological chemistry 85 15964832
2017 Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation. Genes & development 82 28939616
2011 A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line. PLoS genetics 82 21455483
2005 Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains. The EMBO journal 80 15775977
2002 High conservation of the Set1/Rad6 axis of histone 3 lysine 4 methylation in budding and fission yeasts. The Journal of biological chemistry 79 12488447
2006 The multiple faces of Set1. Biochemistry and cell biology = Biochimie et biologie cellulaire 73 16936826
2017 Nup98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells. Genes & development 72 29269482
2011 Contribution of H3K4 methylation by SET-1A to interleukin-1-induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes. Arthritis and rheumatism 70 20862685
2013 Acetylated Histone H3K9 is associated with meiotic recombination hotspots, and plays a role in recombination redundantly with other factors including the H3K4 methylase Set1 in fission yeast. Nucleic acids research 62 23382177
2007 Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans development. Developmental biology 62 17967446
2020 Setd1a Insufficiency in Mice Attenuates Excitatory Synaptic Function and Recapitulates Schizophrenia-Related Behavioral Abnormalities. Cell reports 57 32937141
2011 H3K4 trimethylation by Set1 promotes efficient termination by the Nrd1-Nab3-Sen1 pathway. Molecular and cellular biology 55 21709022
2020 Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome. Molecular psychiatry 54 32346159
2014 The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells. Blood 54 25139354
2017 Targeting human SET1/MLL family of proteins. Protein science : a publication of the Protein Society 53 28160335
2022 Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway. Cell reports 52 35508131
2009 CXXC finger protein 1 restricts the Setd1A histone H3K4 methyltransferase complex to euchromatin. The FEBS journal 52 19951360
2016 Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription. Nature communications 51 27325136
2015 Histone Methyltransferase SET1 Mediates Angiotensin II-Induced Endothelin-1 Transcription and Cardiac Hypertrophy in Mice. Arteriosclerosis, thrombosis, and vascular biology 50 25814673
2020 Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer. Molecular oncology 47 32291851
2014 The SET-2/SET1 histone H3K4 methyltransferase maintains pluripotency in the Caenorhabditis elegans germline. Cell reports 47 25310986
2009 Regulation of H3K4 trimethylation via Cps40 (Spp1) of COMPASS is monoubiquitination independent: implication for a Phe/Tyr switch by the catalytic domain of Set1. Molecular and cellular biology 47 19398585
2006 Structural characterization of Set1 RNA recognition motifs and their role in histone H3 lysine 4 methylation. Journal of molecular biology 46 16787775
2020 The complex activities of the SET1/MLL complex core subunits in development and disease. Biochimica et biophysica acta. Gene regulatory mechanisms 45 32302696
2016 H3K4 Methyltransferase Set1a Is A Key Oct4 Coactivator Essential for Generation of Oct4 Positive Inner Cell Mass. Stem cells (Dayton, Ohio) 45 26785054
2021 An SETD1A/Wnt/β-catenin feedback loop promotes NSCLC development. Journal of experimental & clinical cancer research : CR 44 34645486
2020 The Set1 N-terminal domain and Swd2 interact with RNA polymerase II CTD to recruit COMPASS. Nature communications 42 32358498
2014 Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation. Genes & development 42 24402317
2012 Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases. Epigenetics 42 23235145
2019 Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans. Nucleic acids research 41 31602465
2018 Set1 and Kdm5 are antagonists for H3K4 methylation and regulators of the major conidiation-specific transcription factor gene ABA1 in Fusarium fujikuroi. Environmental microbiology 41 30047187
2016 Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic acids research 41 27141965
2013 Histone H3K27 trimethylation inhibits H3 binding and function of SET1-like H3K4 methyltransferase complexes. Molecular and cellular biology 41 24126056
2012 Yeast Swd2 is essential because of antagonism between Set1 histone methyltransferase complex and APT (associated with Pta1) termination factor. The Journal of biological chemistry 41 22431730
2018 Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nature communications 40 29968706
2014 Feedback control of Set1 protein levels is important for proper H3K4 methylation patterns. Cell reports 40 24613354
2012 CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons. Molecular and cellular biology 40 22907751
2018 The histone methyltransferase SETD1A regulates thrombomodulin transcription in vascular endothelial cells. Biochimica et biophysica acta. Gene regulatory mechanisms 39 29940355
2018 Aberrant expression of SETD1A promotes survival and migration of estrogen receptor α-positive breast cancer cells. International journal of cancer 39 30191958
2016 The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state. Scientific reports 39 27174370
2015 RETRACTED: SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically. Molecular therapy : the journal of the American Society of Gene Therapy 39 26581161
2021 BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency. Nucleic acids research 38 33503260
2019 De Novo and Inherited SETD1A Variants in Early-onset Epilepsy. Neuroscience bulletin 37 31197650
2018 SETD1A protects HSCs from activation-induced functional decline in vivo. Blood 34 29348130
2018 The PHD finger protein Spp1 has distinct functions in the Set1 and the meiotic DSB formation complexes. PLoS genetics 34 29444071
2013 H3K4 methyltransferase Set1 is involved in maintenance of ergosterol homeostasis and resistance to Brefeldin A. Proceedings of the National Academy of Sciences of the United States of America 34 23382196
2019 Taurine Promotes Milk Synthesis via the GPR87-PI3K-SETD1A Signaling in BMECs. Journal of agricultural and food chemistry 33 30678459
2017 Diverse roles of WDR5-RbBP5-ASH2L-DPY30 (WRAD) complex in the functions of the SET1 histone methyltransferase family. Journal of biosciences 33 28229975
2014 Setd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 25550471
2006 Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase. Developmental biology 33 16469305
2020 SET1/MLL family of proteins: functions beyond histone methylation. Epigenetics 32 32795105
2014 Multifaceted genome control by Set1 Dependent and Independent of H3K4 methylation and the Set1C/COMPASS complex. PLoS genetics 32 25356590
2020 Aberrant Cortical Ensembles and Schizophrenia-like Sensory Phenotypes in Setd1a+/- Mice. Biological psychiatry 31 32143831
2017 The C. elegans SET-2/SET1 histone H3 Lys4 (H3K4) methyltransferase preserves genome stability in the germline. DNA repair 31 28779964
2022 Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis. Science advances 30 35245111
2022 H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ. Molecular cell 29 35439434
2020 SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription. Cancers 29 32629770
2017 Binding to RNA regulates Set1 function. Cell discovery 29 29071121
2006 Candida albicans SET1 encodes a histone 3 lysine 4 methyltransferase that contributes to the pathogenesis of invasive candidiasis. Molecular microbiology 29 16629671
2017 RNA Binding by Histone Methyltransferases Set1 and Set2. Molecular and cellular biology 28 28483910
2016 Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers. Epigenetics & chromatin 27 27617035
2015 Physical Interactions and Functional Coordination between the Core Subunits of Set1/Mll Complexes and the Reprogramming Factors. PloS one 27 26691508
2020 Insights on the regulation of the MLL/SET1 family histone methyltransferases. Biochimica et biophysica acta. Gene regulatory mechanisms 24 32304759
2022 The Set1 Histone H3K4 Methyltransferase Contributes to Azole Susceptibility in a Species-Specific Manner by Differentially Altering the Expression of Drug Efflux Pumps and the Ergosterol Gene Pathway. Antimicrobial agents and chemotherapy 23 35471041
2021 SETD1A Mediated H3K4 Methylation and Its Role in Neurodevelopmental and Neuropsychiatric Disorders. Frontiers in molecular neuroscience 23 34803610
2020 SETD1A augments sorafenib primary resistance via activating YAP in hepatocellular carcinoma. Life sciences 23 32918976
2019 The Set1 complex is dimeric and acts with Jhd2 demethylation to convey symmetrical H3K4 trimethylation. Genes & development 21 30842216
2023 MUC1-C intersects chronic inflammation with epigenetic reprogramming by regulating the set1a compass complex in cancer progression. Communications biology 20 37821650
2016 Coordination of Cell Cycle Progression and Mitotic Spindle Assembly Involves Histone H3 Lysine 4 Methylation by Set1/COMPASS. Genetics 20 28049706