Affinage

EZH2

Histone-lysine N-methyltransferase EZH2 · UniProt Q15910

Length
746 aa
Mass
85.4 kDa
Annotated
2026-06-09
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EZH2 is a SET-domain histone methyltransferase that serves as the catalytic engine of Polycomb repressive complex 2 (PRC2), trimethylating histone H3 lysine 27 (H3K27me3) to silence target genes during development and in cancer (PMID:8861097, PMID:29507419). Beyond depositing the repressive H3K27me3 mark, EZH2 functions as a recruitment platform that physically binds DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and is required for DNA methylation at its repressed promoters (PMID:16357870), coupling histone and DNA methylation to enforce stable gene silencing at loci including NTRK1, CD274/IRF1, ACE2, and CDKN2B (PMID:29507419, PMID:31727135, PMID:32291076, PMID:33664859). EZH2 additionally methylates non-histone substrates: it dimethylates SMAD3 at K53/K333 to sustain TGFβ-receptor-driven SMAD3 activation and methylates the pioneer factor FOXA1, both promoting tumor progression (PMID:35085106, PMID:35031563). A partially disordered transactivation domain (SRM/SANT1) sequestered in canonical PRC2 is unlocked by cancer-specific phosphorylation, allowing EZH2 to engage the coactivator p300 and directly activate transcription—for example of DNA-damage-repair genes in castration-resistant prostate cancer—independently of its H3K27me3 repressive activity (PMID:32631994, PMID:35031563). This noncanonical, methyltransferase-independent activator role extends to PRC2-independent complexes with cMyc and HP1BP3 that drive oncogenic transcription, and to a SANT2-dependent maintenance of H3K27 acetylation at the Neat1 promoter promoting inflammasome activation (PMID:36747009, PMID:36517590, PMID:35568718). EZH2 abundance is tightly controlled by post-translational modification: OGT-mediated O-GlcNAcylation at S75 stabilizes the protein and maintains PRC2 integrity (PMID:24474760), PRMT1-mediated dimethylation at R342 blocks CDK1 phosphorylation and TRAF6-dependent degradation (PMID:32895488), and USP7 deubiquitinates and stabilizes EZH2 (PMID:32064169).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Establishing the mammalian ortholog of Drosophila Enhancer of zeste defined EZH2's conserved SET and CXC domain architecture and its developmentally regulated expression, framing it as a candidate epigenetic regulator.

    Evidence cDNA cloning, sequence analysis, and in situ/Northern expression profiling of mouse Enx-1

    PMID:8861097

    Open questions at the time
    • No enzymatic activity demonstrated
    • Substrate and complex membership unknown at this stage
  2. 2000 Medium

    Linking EZH2 expression to hematopoietic proliferation showed it is functionally required for cell division, motivating its study as a proliferation-promoting factor.

    Evidence Antisense knockdown and DNA synthesis assays in stimulated lymphocytes and HL-60 cells

    PMID:10792293

    Open questions at the time
    • Molecular mechanism linking EZH2 to proliferation not defined
    • Single cell-line/single-method
  3. 2005 High

    Discovery that EZH2 physically recruits DNMTs to target promoters connected histone H3K27 methylation to DNA methylation, defining EZH2 as a hub coordinating two repressive epigenetic layers.

    Evidence Reciprocal Co-IP, ChIP, and bisulfite sequencing across multiple target genes

    PMID:16357870

    Open questions at the time
    • Stoichiometry and direct vs indirect DNMT contact not fully resolved
    • Generality across genomic context unaddressed
  4. 2014 High

    Identifying O-GlcNAcylation at S75 revealed that EZH2 protein stability and PRC2 integrity are controlled post-translationally, establishing a nutrient-sensing input to H3K27me3 levels.

    Evidence S75A mutagenesis, OGT knockdown, Co-IP, cosedimentation, mass spectrometry, ChIP

    PMID:24474760

    Open questions at the time
    • Upstream signals controlling OGT targeting of EZH2 unknown
    • Effect on non-canonical EZH2 functions untested
  5. 2018 Medium

    Demonstrating EZH2-driven H3K27me3 repression of NTRK1 in neuroblastoma tied EZH2 to a differentiation-blocking program, with genetic rescue confirming NTRK1 as the functional effector.

    Evidence EZH2 knockdown/inhibitor, ChIP, methylome and transcriptome profiling, neurite extension and NTRK1-depletion rescue

    PMID:29507419

    Open questions at the time
    • Direct vs PRC2-dependent recruitment to NTRK1 not dissected
    • Single lineage context
  6. 2019 Medium

    Showing EZH2 represses PD-L1 and IRF1 via H3K27me3 connected its silencing activity to immune evasion regulation independently of IFNγ-STAT1 signaling.

    Evidence ChIP, dual-luciferase reporter, knockdown, qRT-PCR, flow cytometry in hepatocellular carcinoma

    PMID:31727135

    Open questions at the time
    • Single tumor type
    • Reciprocal validation of recruitment limited
  7. 2020 High

    Structural and biochemical work defined a cryptic transactivation domain that, when unlocked by cancer-specific phosphorylation, recruits p300 — establishing a PRC2-independent transcriptional activator role for EZH2.

    Evidence EZH2-EED crystal structure, NMR, mutagenesis, Co-IP, reporter and cell-based gene expression assays

    PMID:32631994

    Open questions at the time
    • Identity of the specific cancer kinases in vivo not fully mapped
    • Genome-wide activation targets undefined in this study
  8. 2020 High

    Defining the PRMT1–CDK1–TRAF6 PTM-crosstalk axis and USP7-mediated deubiquitination clarified how EZH2 protein levels are stabilized to promote metastasis and tumor growth.

    Evidence In vitro kinase/ubiquitylation assays, site-directed mutagenesis, Co-IP, USP7 catalytic-dead mutant, xenografts

    PMID:32064169 PMID:32895488

    Open questions at the time
    • Interplay between R342 methylation, USP7, and O-GlcNAcylation not integrated
    • Tissue-specificity of these inputs unclear
  9. 2020 Medium

    Mapping E2F1-SUMOylation as a transcriptional activator of the EZH2 promoter and EZH2-driven H3K27me3 repression of ACE2 expanded the regulatory loops governing EZH2 expression and its target repertoire.

    Evidence SAE2 knockdown/SUMO inhibition with ChIP (E2F1) and EZH2 knockout with RNA-seq/ChIP-seq (ACE2)

    PMID:32291076 PMID:32816857

    Open questions at the time
    • Physiological contexts of ACE2 regulation beyond stem cells untested
    • SUMO-EZH2 transcriptional loop generality unknown
  10. 2022 Medium

    A series of studies established EZH2's non-histone methylation (SMAD3, FOXA1) and PRC2-independent activating complexes (cMyc, HP1BP3, SANT2-dependent Neat1 control), reframing EZH2 as a context-dependent activator as well as a repressor.

    Evidence In vitro methylation assays, site mutagenesis, Co-IP/IP-MS, ChIP-seq, ATAC-seq, domain mutants, peptide inhibitors, xenografts

    PMID:35031563 PMID:35085106 PMID:35568718 PMID:36446780 PMID:36517590 PMID:36747009

    Open questions at the time
    • Switch determinants between repressive and activating modes not unified
    • Most activating functions shown in single lineages
    • Structural basis of cMyc/HP1BP3 complexes undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EZH2's distinct PTMs and binding partners are integrated to toggle between PRC2-dependent repression and PRC2-independent transcriptional activation in a given cellular context remains unresolved.
  • No unified model linking phosphorylation/methylation status to repressor-vs-activator output
  • Endogenous prevalence of non-canonical complexes relative to canonical PRC2 not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
DNMT1DNMT3ADNMT3BEEDEP300OGTPRMT1USP7
Complex memberships
PRC2

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 EZH2, within the context of PRC2/3, directly interacts with DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and associates with DNMT activity in vivo. Binding of DNMTs to EZH2-repressed gene promoters depends on EZH2 presence, and EZH2 is required for DNA methylation at those promoters, functioning as a recruitment platform for DNMTs. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), bisulfite genomic sequencing Nature High 16357870
1996 Mouse EZH2 (Enx-1) encodes the murine homolog of Drosophila Enhancer of zeste and contains a conserved SET domain and a newly defined CXC domain. It is expressed ubiquitously in early embryogenesis and becomes restricted to nervous system and hematopoietic sites in later development. cDNA cloning, sequence analysis, in situ hybridization / Northern blot expression analysis Mechanisms of development Medium 8861097
2000 ENX-1 (human EZH2) is required for proliferation of haematopoietic cells: it is upregulated upon T and B lymphocyte stimulation, downregulated upon granulocytic differentiation of HL-60 cells, and antisense knockdown suppresses DNA synthesis in HL-60 cells. Antisense oligodeoxynucleotide knockdown, flow cytometry, [3H]-thymidine incorporation (DNA synthesis assay) British journal of haematology Medium 10792293
2014 OGT-mediated O-GlcNAcylation of EZH2 at serine 75 stabilizes EZH2 protein and maintains PRC2 complex integrity. OGT knockdown specifically reduces EZH2 protein stability and H3K27me3 levels without affecting H3K27 demethylases. The EZH2 S75A mutant shows reduced stability. Co-immunoprecipitation, cosedimentation, site-directed mutagenesis (S75A), OGT knockdown, mass spectrometry, microarray, ChIP Proceedings of the National Academy of Sciences of the United States of America High 24474760
2020 PRMT1 asymmetrically dimethylates EZH2 at R342, which inhibits CDK1-mediated phosphorylation of EZH2 at T345 and T487, thereby attenuating TRAF6-mediated ubiquitylation and proteasomal degradation of EZH2, resulting in EZH2 stabilization and promotion of breast cancer EMT and metastasis. Co-immunoprecipitation, site-directed mutagenesis, in vitro kinase/ubiquitylation assays, mass spectrometry, Western blot, invasion assays, xenograft models Cell death and differentiation High 32895488
2020 EZH2 harbors a partially disordered transactivation domain (TAD) comprising the SRM and SANT1 regions. This TAD mediates protein oligomerization in a non-canonical PRC2 context and is sequestered in canonical PRC2. Cancer-specific phosphorylation events unlock the TAD, enabling interaction with the transcriptional coactivator p300 to activate gene expression. Crystal structure of EZH2-EED binary complex, NMR, mutagenesis, Co-immunoprecipitation, reporter gene assay, cell-based gene expression assays Proceedings of the National Academy of Sciences of the United States of America High 32631994
2022 EZH2 methylates non-histone substrate SMAD3 at K53 and K333. This methylation facilitates SMAD3 interaction with SARA (its membrane localization molecule), sustaining SMAD3 phosphorylation by the TGFβ receptor, thereby promoting SMAD3 activation, tumor metastasis, and poor survival outcomes in breast cancer. In vitro methylation assay, site-directed mutagenesis (K53/K333), Co-immunoprecipitation, TAT-peptide inhibition, xenograft models, patient sample analysis The Journal of clinical investigation High 35085106
2022 EZH2 methylates the pioneer factor FOXA1, contributing to activation of DNA damage repair (BER pathway) genes. EZH2 also interacts with transcriptional coactivator P300 via its transactivation domain to directly drive transcription of DDR genes in castration-resistant prostate cancer, independently of its canonical H3K27me3 repressive function. Gene expression profiling, ChIP-seq, CRISPR-Cas9 knockout screens, Co-immunoprecipitation, in vitro methylation assay Proceedings of the National Academy of Sciences of the United States of America High 35031563
2019 EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma by directly increasing H3K27me3 levels on the promoters of both CD274 (encoding PD-L1) and IRF1 (an essential transcription factor for PD-L1 expression), without affecting IFNγ-STAT1 pathway activation. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, EZH2 knockdown, quantitative RT-PCR, Western blot, flow cytometry Journal for immunotherapy of cancer Medium 31727135
2021 EZH2 interacts with cMyc in a PRC2- and H3K27me3-independent manner in multiple myeloma cells, co-localizing with gene activation-associated marks to promote oncogenic transcription. This noncanonical EZH2-cMyc complex is distinct from the canonical EZH2-PRC2 repressive complex. Co-immunoprecipitation, ChIP-seq, EZH2 PROTAC degrader (MS177), RNA-seq, proliferation assays, xenograft models Oncogene Medium 36747009
2021 PRMT5 physically interacts with EZH2, leading to enhanced EZH2 binding and H3K27me3 deposition at the CDKN2B (p15INK4b) promoter and epigenetic repression of CDKN2B to promote colorectal cancer progression. Co-immunoprecipitation, GST pulldown, ChIP assay, bisulfite sequencing, luciferase reporter assay Theranostics Medium 33664859
2020 USP7 deubiquitinates and stabilizes EZH2 protein. Overexpression of USP7 promotes EZH2 protein levels while a catalytically dead USP7 mutant does not; USP7 knockdown reduces EZH2 protein. USP7/EZH2 axis promotes cell growth, invasion and tumor formation. Co-immunoprecipitation, ubiquitination assay, USP7 knockdown/overexpression, site-directed mutagenesis of USP7 catalytic residue, in vivo xenograft American journal of cancer research Medium 32064169
2020 EZH2-mediated H3K27me3 at the ACE2 promoter region represses ACE2 expression. Knockout of EZH2 in human embryonic stem cells results in significantly increased ACE2 expression, accompanied by decreased H3K27me3 and increased H3K27ac at the ACE2 promoter. EZH2 knockout, RNA-seq, ChIP-seq Biochemical and biophysical research communications Medium 32291076
2022 EZH2 interacts with HP1BP3 in glioma stem cells, impairing H3K9 methylation, and EZH2-HP1BP3 co-activate WNT7B expression, thereby increasing temozolomide resistance and stemness of glioblastoma cells. Immunoprecipitation and mass spectrometry, co-immunoprecipitation, ChIP, RNA-seq, overexpression/knockdown, in vivo xenograft Oncogene Medium 36517590
2022 EZH2-mediated H3K27me3 promotes KRT14 transcription (rather than repression) in TNBC by attenuating binding of the transcriptional repressor SP1 to the KRT14 promoter, representing a non-canonical gene-activating function of H3K27me3/EZH2. ChIP assay, EZH2 knockdown, EZH2 inhibitor (EPZ6438), in vivo peritoneal metastasis model, SP1 binding assay Nature communications Medium 36446780
2018 EZH2 regulates NTRK1 (TrkA) expression via H3K27me3 modifications at the NTRK1 P1 promoter region in neuroblastoma, repressing NTRK1 transcript variants 1/2. EZH2 knockdown or inhibition induces NTRK1 expression and neuroblastoma cell differentiation; NTRK1 depletion cancels this differentiation. EZH2 lentiviral knockdown, ChIP assay, transcriptome microarray, bisulfite methylome analysis, EZH2 inhibitor treatment, neurite extension assay Oncogene Medium 29507419
2022 Ezh2 promotes inflammasome activation in macrophages/microglia independently of its methyltransferase activity. Via its SANT2 domain, Ezh2 maintains H3K27 acetylation at the Neat1 lncRNA promoter, promoting chromatin accessibility and p65-mediated Neat1 transcription. p53 competes with Ezh2 at this promoter; loss of Ezh2 allows p53 to recruit SIRT1 for H3K27 deacetylation, suppressing Neat1 and inflammasome activation. ChIP, ATAC-seq, EZH2 knockdown/domain mutant, promoter-reporter assay, Co-immunoprecipitation, in vivo mouse models Cell death and differentiation Medium 35568718
2020 SUMOylation of E2F1 enhances its binding to the EZH2 promoter, transcriptionally activating EZH2. Knockdown of the SUMO-activating enzyme SAE2 or pharmacologic SUMOylation inhibition reduces EZH2 mRNA, protein, and H3K27me3 levels. SAE2 knockdown, pharmacologic SUMOylation inhibition, ChIP, quantitative RT-PCR, Western blot, gene expression analysis across >6500 tumors Cancer research Medium 32816857

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The Polycomb group protein EZH2 directly controls DNA methylation. Nature 1727 16357870
2020 EZH2: a novel target for cancer treatment. Journal of hematology & oncology 732 32723346
2008 Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutation research 716 18723033
2011 Aberrations of EZH2 in cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 443 21367748
2011 The role of EZH2 in tumour progression. British journal of cancer 291 22187039
2014 Regulation and Role of EZH2 in Cancer. Cancer research and treatment 241 25038756
2013 The Fusarium graminearum histone H3 K27 methyltransferase KMT6 regulates development and expression of secondary metabolite gene clusters. PLoS genetics 208 24204317
2011 EZH2 methyltransferase and H3K27 methylation in breast cancer. International journal of biological sciences 201 22211105
2020 EZH2-Targeted Therapies in Cancer: Hype or a Reality. Cancer research 199 32978169
2014 O-GlcNAcylation regulates EZH2 protein stability and function. Proceedings of the National Academy of Sciences of the United States of America 196 24474760
2017 Targeting EZH2 in cancer therapy. Current opinion in oncology 178 28665819
2019 EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma. Journal for immunotherapy of cancer 152 31727135
2018 Enhancer of zeste homolog 2 (EZH2) inhibitors. Leukemia & lymphoma 149 29473431
2013 EZH2 in normal and malignant hematopoiesis. Leukemia 149 24097338
2020 Methylation of EZH2 by PRMT1 regulates its stability and promotes breast cancer metastasis. Cell death and differentiation 144 32895488
2012 EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer metastasis reviews 135 22711031
2022 Tazemetostat: EZH2 Inhibitor. Journal of the advanced practitioner in oncology 131 35369397
2023 The roles of EZH2 in cancer and its inhibitors. Medical oncology (Northwood, London, England) 123 37148376
2015 Diverse involvement of EZH2 in cancer epigenetics. American journal of translational research 122 25901190
2022 EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis. Nature communications 110 36446780
2015 Targeting EZH2 and PRC2 dependence as novel anticancer therapy. Experimental hematology 95 26027790
2019 Inhibition of EZH2 prevents fibrosis and restores normal angiogenesis in scleroderma. Proceedings of the National Academy of Sciences of the United States of America 93 30755532
2016 EZH2 in normal hematopoiesis and hematological malignancies. Oncotarget 91 26497210
2018 Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer. Molecular cancer therapeutics 90 29726819
2014 EZH2: not EZHY (easy) to deal. Molecular cancer research : MCR 90 24526064
2019 Long noncoding RNA Neat1 modulates myogenesis by recruiting Ezh2. Cell death & disease 88 31243262
2021 Going beyond Polycomb: EZH2 functions in prostate cancer. Oncogene 85 34349243
2022 Targeting EZH2 for cancer therapy: From current progress to novel strategies. European journal of medicinal chemistry 83 35569264
2018 Emerging EZH2 Inhibitors and Their Application in Lymphoma. Current hematologic malignancy reports 83 30112706
2020 EZH2 function in immune cell development. Biological chemistry 82 32045348
2016 Knock-down of the methyltransferase Kmt6 relieves H3K27me3 and results in induction of cryptic and otherwise silent secondary metabolite gene clusters in Fusarium fujikuroi. Environmental microbiology 82 27348741
2021 The noncanonical role of EZH2 in cancer. Cancer science 79 33615636
2016 Regulation of T Cell Differentiation and Function by EZH2. Frontiers in immunology 76 27199994
2019 EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications. Journal of hematology & oncology 73 31752930
2022 Circular EZH2-encoded EZH2-92aa mediates immune evasion in glioblastoma via inhibition of surface NKG2D ligands. Nature communications 70 35970825
2014 Targeting histone methyltransferase EZH2 as cancer treatment. Journal of biochemistry 70 25179367
2007 Expression of polycomb group protein EZH2 in nevi and melanoma. Journal of cutaneous pathology 70 17640228
2021 PRMT5 functionally associates with EZH2 to promote colorectal cancer progression through epigenetically repressing CDKN2B expression. Theranostics 68 33664859
2020 Post-translational modifications of EZH2 in cancer. Cell & bioscience 68 33308321
2017 Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma. Histopathology 67 27859460
1996 Isolation and developmental expression analysis of Enx-1, a novel mouse Polycomb group gene. Mechanisms of development 66 8861097
2018 EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications. Oncogene 64 29507419
2020 lncRNA HOTAIR Promotes DNA Repair and Radioresistance of Breast Cancer via EZH2. DNA and cell biology 58 33136445
2015 Targeting EZH2 for cancer therapy: progress and perspective. Current protein & peptide science 56 25854924
2014 The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma. Journal of hepatology 55 24845612
2013 Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond. Epigenetics 55 23644490
2020 A partially disordered region connects gene repression and activation functions of EZH2. Proceedings of the National Academy of Sciences of the United States of America 54 32631994
2020 EZH2 deficiency attenuates Treg differentiation in rheumatoid arthritis. Journal of autoimmunity 53 31952907
2020 EZH2-mediated H3K27me3 inhibits ACE2 expression. Biochemical and biophysical research communications 53 32291076
2015 EZH2 in Bladder Cancer, a Promising Therapeutic Target. International journal of molecular sciences 52 26580594
2024 AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution. Nature 51 39385030
2020 EZH2 in Myeloid Malignancies. Cells 51 32650416
2022 DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma. Cancer letters 49 36087682
2022 Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress. Proceedings of the National Academy of Sciences of the United States of America 48 35031563
2021 Targeting EZH2 as cancer therapy. Journal of biochemistry 45 33479735
2022 EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis. The Journal of clinical investigation 44 35085106
2017 EZH2-, CHD4-, and IDH-linked epigenetic perturbation and its association with survival in glioma patients. Journal of molecular cell biology 44 29272522
2024 EZH2-mediated development of therapeutic resistance in cancer. Cancer letters 42 38331087
2019 Role of EZH2 in cell lineage determination and relative signaling pathways. Frontiers in bioscience (Landmark edition) 42 30844722
2014 EZH2: an emerging role in melanoma biology and strategies for targeted therapy. Pigment cell & melanoma research 42 24912396
2016 Role of EZH2 histone methyltrasferase in melanoma progression and metastasis. Cancer biology & therapy 40 27105109
2022 Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation. Cell death and differentiation 36 35568718
2022 The role of EZH1 and EZH2 in development and cancer. BMB reports 35 36476271
2024 NOP2 facilitates EZH2-mediated epithelial-mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression. Cell death & disease 32 39013911
2021 AP-2α-Mediated Activation of E2F and EZH2 Drives Melanoma Metastasis. Cancer research 32 34210752
2020 Targeting epigenetics in sarcomas through EZH2 inhibition. Journal of hematology & oncology 32 32264965
2023 EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain. Cells 31 37048131
2023 Non-canonical functions of EZH2 in cancer. Frontiers in oncology 31 37664059
2024 Discovery of a novel, highly potent EZH2 PROTAC degrader for targeting non-canonical oncogenic functions of EZH2. European journal of medicinal chemistry 30 38295690
2022 EZH2-CCF-cGAS Axis Promotes Breast Cancer Metastasis. International journal of molecular sciences 30 35163710
2020 Ezh2 Ameliorates Osteoarthritis by Activating TNFSF13B. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30 31910305
2019 Clinical and biological significance of EZH2 expression in endometrial cancer. Cancer biology & therapy 29 31640461
2000 Proliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells. British journal of haematology 29 10792293
2023 EZH2: An Accomplice of Gastric Cancer. Cancers 27 36672374
2021 NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer. Communications biology 27 33750924
2021 Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network. International journal of biological sciences 27 34512145
2022 Downregulation of MEG3 and upregulation of EZH2 cooperatively promote neuroblastoma progression. Journal of cellular and molecular medicine 26 35257481
2020 Both EZH2 and JMJD6 regulate cell cycle genes in breast cancer. BMC cancer 26 33246425
2016 EZH2 as a mediator of treatment resistance in melanoma. Pigment cell & melanoma research 26 27063195
2017 Aberrant expression of ALK and EZH2 in Merkel cell carcinoma. BMC cancer 25 28359267
2022 Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumors. Molecular cancer therapeutics 24 35247919
2021 EZH2 as an Epigenetic Regulator of Cardiovascular Development and Diseases. Journal of cardiovascular pharmacology 24 34029268
2020 SUMOylation of E2F1 Regulates Expression of EZH2. Cancer research 24 32816857
2022 EZH2 Mediates Proliferation, Migration, and Invasion Promoted by Estradiol in Human Glioblastoma Cells. Frontiers in endocrinology 23 35197928
2017 Double sword role of EZH2 in leukemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 29289837
2022 EZH2 interacts with HP1BP3 to epigenetically activate WNT7B that promotes temozolomide resistance in glioblastoma. Oncogene 22 36517590
2020 USP7 stabilizes EZH2 and enhances cancer malignant progression. American journal of cancer research 22 32064169
2023 Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader. Oncogene 21 36747009
2022 EZH2 Inhibitors: The Unpacking Revolution. Cancer research 21 35110396
2020 Analysis of TET2 and EZH2 gene functions in chromosome instability in acute myeloid leukemia. Scientific reports 21 32066746
2020 EZH2 as a Potential Target for NAFLD Therapy. International journal of molecular sciences 20 33207561
2017 Functional and therapeutic significance of EZH2 in urological cancers. Oncotarget 20 28410242
2012 The role of histone methyltransferase EZH2 in myelodysplastic syndromes. Expert review of hematology 20 22475286
2023 Review: Targeting EZH2 in neuroblastoma. Cancer treatment reviews 19 37467626
2023 Cellular senescence primes liver fibrosis regression through Notch-EZH2. MedComm 19 37614965
2021 Myeloid Ezh2 Deficiency Limits Atherosclerosis Development. Frontiers in immunology 19 33574814
2023 Targeting EZH2 in SMARCB1-deficient sarcomas: Advances and opportunities to potentiate the efficacy of EZH2 inhibitors. Biochemical pharmacology 18 37541451
2022 Covalent inhibitors of EZH2: Design, synthesis and evaluation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 34998031
2022 BMP2 inhibits cell proliferation by downregulating EZH2 in gastric cancer. Cell cycle (Georgetown, Tex.) 17 35856444
2020 The functions of EZH2 in immune cells: Principles for novel immunotherapies. Journal of leukocyte biology 17 33040370

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