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General Information
Name
viral infection, susceptibility to (postulated), EHMT-related
FlyBase ID
FBhh0000597
Disease Ontology Term
Parent Disease
OMIM
Overview

In humans, many aspects of the interferon-induced anti-viral response are mediated by the JAK-STAT signaling pathway. Experiments in Drosophila characterizing tolerance to RNA virus infection have led to the identification of an epigenetic mechanism, involving the Drosophila histone H3 lysine 9 methyltransferase G9a, that modulates the viral-infection-induced response of the JAK-STAT signaling pathway. There are two genes orthologous to Dmel\G9a in human, EHMT1 and EHMT2. Classical loss-of-function mutations, RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated for Dmel\G9a. The human EHMT1 is implicated in Kleefstra syndrome (OMIM:610253; FBhh0000556).

Neither human gene has been introduced into flies.

Animals homozygous for an amorphic mutation of Dmel\G9a survive to adulthood and are fertile, however, they are more sensitive to RNA virus infection; reduced adult lifespan is observed for G9a-deficient virus-infected flies. Multiple viruses were tested (introduced by intra-thoracic injection); increased susceptibility was observed for all RNA viruses tested, but not for the single DNA virus tested. Physical and genetic interactions of G9a have been described; see below and in the G9a gene report.

[updated Sep. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: viral infection, susceptibility to (postulated), EHMT-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

The interferon (IFN) induced anti-viral response is among the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon-stimulated genes (ISGs) (Fleming, 2016; pubmed:27367734).

Results in Drosophila identify an epigenetic mechanism underlying tolerance to virus infection. The Drosophila histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by modulating the response of the JAK-STAT signaling pathway. G9a-deficient mutants are more sensitive to RNA virus infection; early lethality is observed in G9a-deficient virus-infected flies.

Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; the human genes are EHMT1 and EHMT2.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; the human genes are EHMT1 and EHMT2.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      G9a (G9a) encodes a histone-lysine methyltransferase involved in epigenetic regulation. It contributes to multiple processes including gene expression, dendrite morphogenesis, larval locomotory behavior as well as short and long-term memory. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human EHMT2 and EHMT1 (1 Drosophila to 2 human); there are lower-scoring orthologs in both species. Dmel\G9a shares 26-28% identity and 41-42% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (8 groups)
      protein-protein
      Interacting group
      Assay
      References
      molecular sieving, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      enzymatic study, autoradiography
      pull down, anti tag western blot
      pull down, anti tag western blot
      tandem affinity purification, Identification by mass spectrometry
      pull down, anti tag western blot
      Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      ends-out gene targeting
      Delta2-3 transposase
      Delta2-3 transposase
      P-element activity
      References (6)