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FLASH GENE
Symbol EHMT2 contributors: mct/pgu - updated : 16-06-2019
HGNC name euchromatic histone-lysine N-methyltransferase 2
HGNC id 14129
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven ANK repeats
  • one post-SET domain
  • one pre-SET domain
  • one SET domain
    • HOMOLOGY
    interspecies homolog to murine Ehmt2 (95.6pc)
    homolog to rattus Ehmt2 (95.9pc)
    Homologene
    FAMILY histone-lysine methyltransferase family, Suvar3-9 subfamily
    CATEGORY adaptor , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,euchromosome
    text
  • expressed in the nucleus in undifferentiated myoblasts and remained nuclear, albeit at much lower expression, in MHC+ differentiated cells
    • basic FUNCTION
  • may be involved in intracellular protein-protein interaction
  • lysine-preferring histone methyltransferase activity
  • silencing NRSF target genes in nonneuronal cells by generating a highly localized domain of dimethylated histone H3-K9 around NRSEs
  • functioning as a transcriptional corepressor in association with a CDP/cut complexor in association with GFI1 and HDAC1
  • promotes binding of DNA methyltransferases and the G9a/GLP complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation
  • is a SET-domain mammalian histone methyltransferase responsible for mono- and dimethylation of lysine 9 in histone H3 (H3K9) at euchromatic regions
  • dual role in maintaining proper expression (both repression and activation) of the beta-globin genes in differentiating adult erythroid cells
  • gatekeeper for a specific set of genes localized within the late replicating nuclear periphery
  • responsible for the majority of dimethylation of histone H3 at lysine 9 (H3K9me2) and is required for the efficient repression of developmentally regulated genes during embryonic stem cell differentiation
  • unpredicted and complex roles in regulating gene expression during lineage commitment in adult CD4(+) T cells
  • histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes
  • promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule EPCAM
  • promotes binding of DNA methyltransferases and the EHMT2 complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation)
  • H3K9 KMTase, required for the establishment, but not for the maintenance, of silencing of newly integrated proviruses
  • histone lysine methyltransferase localized in euchromatin regions and acting as a corepressor for specific transcription factors
  • its dysregulation plays an important role in the growth regulation of cancer cells
  • unconventional epigenetic mechanism that connects EHMT2 to maintenance of an undifferentiated fate by methylation of MYOD1
  • HDAC5, HDAC7, and EHMT2 are involved in the transcriptional repression activity of PARP2
  • EHMT1, EHMT2 have an essential role in normal morphogenesis of the atrioventricular septum through regulation of the size of the atrioventricular cushion
  • EHMT2 is an epigenetic regulator of VEGFA alternative splicing
  • EHMT1, EHMT2 are epigenetic regulators involved in gamma-globin repression
  • orchestrates PHF19 and KDM7A to promote histone H3K27 methylation
  • EHMT1 and EHMT2 are differentially expressed in cortical areas
  • EHMT1 and EHMT2 are DDR components, with implications for genome-integrity maintenance through proper dynamic methylation of MDC1
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2
  • EHMT2 and EHMT1 are critical components of the DNA repair pathway, and promote responses to DNA damage
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CUTL1
  • interacting with GFI1
  • interacting with ESCO2
  • EHMT2/EHMT1-associating zinc finger molecule named WIZ that can interact with EHMT2 and EHMT1 independently but is more stable in the EHMT2/EHMT1 heteromeric complexes
  • binding partner of ZNF200
  • CEBPB is a direct substrate of EHMT2-mediated post-translational modification that alters the functional properties of CEBPB during gene regulation
  • interacting with UHRF1 (may serve as a focal point of transcriptional regulation mediated by EHMT2 and other chromatin modification enzymes)
  • RUVBL2 is methylated at lysine 67 in hypoxic conditions by the methyltransferase EHMT2
  • interaction with HELLS (promotes binding of DNA methyltransferases and the EHMT2 complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation)
  • interaction with HELL (HELL promotes binding of DNA methyltransferases and the EHMT2 complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation)
  • unique inhibitor of skeletal muscle differentiation that plays a dominant role in MYOD1 activation
  • functioned as a positive regulator for RUNX2 target genes
  • EHMT2 mediates NFIL3-dependent suppression of hepatic FGF21 by enhancing histone methylation (H3K9me2) of the FGF21 promoter
  • PARP2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase EHMT2 to the promoters of cell cycle-related genes, generating repressive chromatin signatures
  • ZNF644 interact with the transcription activation domain of EHMT2
  • WIZ regulates global H3K9me2 levels by facilitating the interaction of EHMT2 with chromatin
  • EHMT1 and EHMT2 are novel regulators of MDC1, which is required for the accumulation of DNA damage response (DDR) factors
  • TBC1D3 interacts with EHMT2 a, a euchromatic histone lysine N-methyltransferase, which mediates dimethylation of histone 3 in lysine 9 (H3K9me2), a suppressive mark for gene expression
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    significantly elevated in bladder carcinomas compared with nonneoplastic bladder tissues
    tumoral     --over  
    in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis
    constitutional     --over  
    in the peripheral blood cells may support the notion of a restrictive chromatin state in autism spectrum disorders (ASD), similar to schizophrenia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    importance of EHMT2 as a promising therapeutic target for various types of cancer
    bloodhemoglobin 
    novel therapeutic target for sickle cell disease (SCD)
    ANIMAL & CELL MODELS