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Symbol EZH2 contributors: mct/shn - updated : 24-05-2017
HGNC name enhancer of zeste homolog 2 (Drosophila)
HGNC id 3527
Corresponding disease
WVSS2 Weaver-Smith syndrome 2
Location 7q36.1      Physical location : 148.504.474 - 148.581.414
Synonym name
  • lysine N-methyltransferase 6
  • enhancer of zeste 2
  • enhancer of zeste (Drosophila) homolog 2
  • Synonym symbol(s) EZR2, ENX1, EZH1, ENX-1, KMT6, MGC9169
    TYPE functioning gene
    STRUCTURE 76.98 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D7S2442 - D7S2419 - EZH2 - D7S2426 - D7S505 - qter
    regionally located within a critical region for malignant myeloid disorders
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 splicing 2723 85.9 751 - 2000 10780782
    19 splicing 2563 80.9 707 - 2000 10780782
  • lacking two in-frame segments in the coding region compared to variant 1
  • 19 splicing 2682 - 695 - -
    20 splicing 2681 - 737 - -
    20 splicing 2708 - 746 - -
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly Homo sapiens
    Digestiveliver   moderately Homo sapiens
    Nervousbrainforebraincerebral cortex   Homo sapiens
    Reproductivefemale systemplacenta  highly Homo sapiens
    Respiratorylung   highly Homo sapiens
    Urinarykidney   lowly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    Muscularstriatumcardiac   Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell
    Muscularmyocyte Homo sapiens
    cell lineage abundant in normal germinal center B cells
    cell lines
    at STAGE
    Text fetal brain, lung, liver and kidney
  • a nuclear localization signal
  • one SET domain, required for early B-cell development, and essential for the methyltransferase activity of EZH2
  • two SANT domains
  • a C-rich domain
  • conjugated PhosphoP
    mono polymer complex
    interspecies homolog to Drosophila enhancer of zeste 2
    ortholog to Ezh2, Mus musculus
    ortholog to Ezh2, Rattus norvegicus
    ortholog to EZH2, Pan troglodytes
    intraspecies paralog to EZH1
  • Polycomb-group (PcG) family
  • CATEGORY enzyme , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • transcriptional repressor in tumor cells activated as they become metastatic
  • playing a role in vascular invasion and breast cancer metastasis
  • implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer
  • exerting its epigenetic function through regulation of histone methylation
  • a critical role in early B cell development and rearrangement of the immunoglobulin heavy chain gene and a key regulator of histone H3 methylation in early B cell progenitors (
  • regulation of actin polymerization (
  • may be involved in the regulation of gene transcription and chromatin structure
  • acting as a methyltransferase
  • may play a role in the hematopoietic and central nervous systems
  • required for DNA methylation of EZH2-target promoters
  • regulates muscle gene expression and skeletal muscle differentiation (
  • serves as a recruitment platform for DNA methyltransferases (
  • EZH1, EZH2 maintain repressive chromatin through different mechanisms
  • might have a central role in Ewing tumor pathology by shaping the oncogenicity and stem cell phenotype of this tumor
  • important in ER-negative breast cancer growth
  • histone methyltransferase that constitutes the catalytic unit of the polycomb repressive complex 2 (PRC2)
  • catalytic subunit of the polycomb repressive complex 2 (PRC2), a highly conserved histone H3 lysine 27 (H3K27) methyltransferase that influences stem cell renewal by epigenetic repression of genes involved in cell fate decisions
  • acting as a tumor suppressor for myeloid malignancies
  • acts as a codominant tumor suppressor for myelopoiesis )
  • essential for controlling the rate at which development progresses within cortical progenitor cell lineages
  • catalytic subunit of the PRC2 Polycomb complex and mediates transcriptional repression through its histone methyltransferase activity
  • involved in regulating a specific epigenetic program in normal germinal centers, including silencing of antiproliferative genes, which may contribute to the malignant transformation of germinal center B cells into diffuse large B-cell lymphoma
  • regulates stem cells renewal, maintenance, and differentiation into different cell lineages including neuron
  • stabilizes transcription by depositing repressive marks during development that persist into adulthood
  • negatively regulates Intracellular Ca2+ through suppression of PIP5K1C
  • acts as an oncogene in tumorigenesis of ovarian cancer with the possible mechanism to suppress the anti-oncogene CDKN1C
  • EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair
  • downregulates the important genes such as CDH1 and RUNX3 by increasing histone H3K27 trimethylation
  • an upstream regulator of anteroposterior prepattern at an early stage essential for cell survival and proximodistal segment elongation
  • required for pancreatic beta-cell expansion and metabolic changes from PDGFRA activation in beta-cells
  • triggers transcriptional repression by catalyzing the addition of methyl groups onto lysine 27 of histone H3 (H3K27me2/3)
  • might be an oncogene with transforming activity that is linked to dysregulated cellular memory and transcriptional repression
  • is required to stabilize postnatal cardiac gene expression
  • modulates a feed-forward pathway that represses fetal gene expression and is reinforced by repression of SIX1
  • UHRF1 along with EZH2 coordinate epigenetic silencing of tumour suppressor genes in prostate tumours
  • is involved in repressing gene expression through methylation of histone H3 on lysine 27 (H3K27)
  • mediates histone H3K27 trimethylation and is associated with gene silencing, coordinately expressed and function upstream of WHSC1, which mediates H3K36 dimethylation and is associated with active transcription
  • PRC2-EZH2 is important for the establishment of H3K27me3 in dividing cells, whereas PRC2-EZH1 is required for its maintenance in resting cells
  • critical redundancy of EZH1 and EZH2 in maintaining hepatic homeostasis and regeneration
  • EZH2-mediated BBC3 gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis
  • EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression
  • in neonatal heart regeneration, EZH1 was required, but EZH2 was dispensable
  • EZH2 is a critical regulator of genomic stability at stalled forks that couples histone modifications to nuclease recruitment
  • EZH2 has a dual function in tumorigenesis as an oncogene and tumor suppressor gene
  • CELLULAR PROCESS nucleotide, chromatin organization
  • establishment and/or maintenance of chromatin architecture
  • essential role in promoting histone H3 lysine 27 trimethylation and epigenetic gene silencing
    oncogenic pathway that functionally links FGF2 with EZH2 via KDM2B and miR-101
    a component
  • cytosolic Ezh2-containing methyltransferase complex
  • component of a novel EED-PHF1 complex and demonstrate its important role in H3K27 methylation and Hox gene silencing
  • SAFB formed a complex with the histone methyltransferase EZH2 at AR-interacting chromatin sites in association with other polycomb repressive complex 2 (PRC2) proteins
  • part of polycomb repressive complex 2 (PRC2)
  • EZH1 and EZH2 form similar PRC2 complexes but exhibit contrasting repressive roles
  • part of PRC2 complex containing four core components: EZH2, EED, SUZ12, and RBBP7
  • EZH2-WHSC1 HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis
  • MSMB gene
  • RUNX3 gene promoter
  • promoter region of PIP5K1C
  • RNA
    small molecule
  • vav 1 guanine nucleotide exchange factor, VAV1
  • alpha thalassemia/mental retardation syndrome X-linked, ATRX via the SET domain
  • Extra Sex Combs, ESC
  • pRb2/p130
  • embryonic ectoderm development, EED
  • transcriptional regulator YY1
  • polycomb homolog 1, EPC1
  • Polycomb repressive complexes 2 and 3
  • estrogen receptor activity, REA
  • Nuclear inhibitor of Protein phosphatase 1, NIPP1
  • BRCA1 is required for the proliferative effects of EZH2
  • Not dead yet-1, Ndy1
  • beta-catenin
  • EED, SUZ12 and RBBP4
  • SLIT2
  • KDM2B
  • KLF2 repression has an important role in EZH2 oncogenesis
  • PDGFRA regulates pancreatic beta-cell EZH2 expression and proliferation
  • EZH2-mediated repression of SIX1 in differentiating cardiac progenitors is essential for stable gene expression and homeostasis in the postnatal heart
  • required for the transient repression of HES1 in erythroid cells
  • SOX4 is a master regulator of EMT by governing the expression of the epigenetic modifier EZH2
  • EZH1 and EZH2 have antagonistic roles in regulating DLG4 transcription
  • both EZH2 and KDM6A were shown to affect expression of master regulatory genes involved in adipogenesis and osteogenesis and H3K27me3 on the promoters of master regulatory genes
  • NFIB binds to the EZH2 promoter and overexpression of NFIB represses EZH2 transcription
  • contributes to the development of esophageal squamous cell carcinoma (ESCC) by interacting with EZH2 to promote methylation of POU3F3, which encodes a transcription factor
  • MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of SORBS2
  • NOS2 is a potential target of the histone methyltransferase EZH2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3)
  • EZH2 directly binds to the BBC3 promoter thus epigenetic repression of BBC3 expression
  • EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration
  • EZH2 localizes at stalled forks where it methylates Lys27 on histone 3 (H3K27me3), mediating recruitment of the MUS81 nuclease
  • TET1 is found to recruit the co-repressor proteins, SIN3A and the histone lysine methyltransferase, EZH2 to osteogenic genes
  • interaction between NUDT21 and EZH2 may play an important role in the crosstalk between alternative polyadenylation (APA) and miRNA-mediated gene silencing in Preeclampsia
  • MELK induces EZH2 phosphorylation, which subsequently binds to and methylates NFKB1, leading to tumor proliferation and persistence of stemnessin glioma
  • important role of MELK and USP36 in mediating EZH2 stability in natural killer/T-cell lymphoma (NKTL)
  • cell & other
    Other phosphorylated by AKT1 (
    phosphorylated by cyclin-dependent kinase 1 and cyclin-dependent kinase 2
    corresponding disease(s) WVSS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    gain function in mantle lymphoma and in prostate cancer (metastatic)
    tumoral     --over  
    overexpressed in aggressive breast cancer
    tumoral     --over  
    in melanoma, prostate, and endometrial carcinoma with invasive growth and aggressive clinical behavior
    tumoral     --over  
    in Ewing tumors
    constitutional       gain of function
    at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis
    tumoral somatic mutation      
    ffecting a single tyrosine (Tyr641) in the EZH2 SET domain and have associated these with Follicular lymphoma (FL) and the germinal center B cells subtype of diffuse large B-cell lymphoma (DLBCL)
    tumoral somatic mutation      
    in myelodysplastic syndromes
    tumoral somatic mutation      
    EZH2 mutations are independently associated with shorter survival in patients with primary myelofibrosis
    tumoral     --other  
    aberrant induction of Ezh2 is an early and initiating event in pancreatic carcinogenesis as observed even in proliferative lesions such as dysplasia
    tumoral germinal mutation     loss of function
    in patients with myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and MDS/MPN overlap disorders
    tumoral     --over  
    in ovarian cancer and is associated with tumor metastasis and poor survival
    Susceptibility to myelodisplastic syndrome
    Variant & Polymorphism other
  • Y641C mutation has been reported to dramatically reduce enzymatic activity, and is associated to myelodisplastic syndrome
  • Candidate gene prognostic marker in endometrial cancer
    Therapy target
    EZH2 and EZH2-mediated events are promising novel targets for Ewing tumor therapy
    may provide a prime target to prevent and/or halt ER-negative breast cancer progression
    might be a useful drug target in AML (acute myeloid leukemia)
    activation of intracellular Ca2+ signaling by repressing EZH2 might be a potential strategy to promote neuronal differentiation from hMSCs for application to neurological dysfunction diseases
    potential target for tumor therapy
    EZH2 inhibition is potentially an efficient treatment for more aggressive breast cancers
    potential therapeutic target for treatment of ovarian cancer
    histone modifier EZH2 is a strong candidate of target for successful applications in pancreatic cancer therapeutics
    pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma
  • mice deficient for Ezh2 die at early stages of development by failing to complete gastrulation
  • conditional deletion of beta-cell Ezh2 in juvenile mice reduced H3 trimethylation at the Ink4a/Arf locus, leading to precocious increases of p16(INK4a) and p19(Arf), reduced beta-cell proliferation and mass, hypoinsulinemia, and mild diabetes (
  • hematopoietic-specific deletion of Ezh2 in mice induced heterogeneous hematopoietic malignancies