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Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the EHMT2 gene.[5][6][7] G9a catalyzes the mono- and di-methylated states of histone H3 at lysine residue 9 (i.e., H3K9me1 and H3K9me2) and lysine residue 27 (H3K27me1 and HeK27me2).[8][9]

Protein EHMT2 PDB 2o8j.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesEHMT2, BAT8, C6orf30, G9A, GAT8, KMT1C, NG36, euchromatic histone lysine methyltransferase 2
External IDsOMIM: 604599 MGI: 2148922 HomoloGene: 48460 GeneCards: EHMT2
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 6: 31.88 – 31.9 MbChr 17: 35.12 – 35.13 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse


A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described.[7]

G9a and G9a-like protein, another histone-lysine N-methyltransferase, catalyze the synthesis of H3K9me2, which is a repressive mark.[8][9][10] G9a is an important control mechanism for epigenetic regulation within the nucleus accumbens (NAcc);[11] reduced G9a expression in the NAcc plays a central role in mediating the development of an addiction.[11] G9a opposes increases in ΔFosB expression via H3K9me2 and is suppressed by ΔFosB.[11][12] G9a exerts opposite effects to that of ΔFosB on drug-related behavior (e.g., self-administration) and synaptic remodeling (e.g., dendritic arborization – the development of additional tree-like dendritic branches and spines) in the nucleus accumbens, and therefore opposes ΔFosB's function as well as increases in its expression.[11] G9a and ΔFosB share many of the same gene targets.[13] In addition to its role in the nucleus accumbens, G9a play a critical role in the development and the maintenance of neuropathic pain.[14][15] Following peripheral nerve injury, G9a regulates the expression of +600 genes in the dorsal root ganglia. This transcriptomic change reprograms the sensory neurons to a hyperexcitable state leading to mechanical pain hypersensitivity. [14]


EHMT2 has been shown to interact with KIAA0515 and the prostate tissue associated homeodomain protein NKX3.1.[16][17]


  1. ^ a b c ENSG00000224143, ENSG00000206376, ENSG00000204371, ENSG00000227333, ENSG00000232045, ENSG00000236759 GRCh38: Ensembl release 89: ENSG00000238134, ENSG00000224143, ENSG00000206376, ENSG00000204371, ENSG00000227333, ENSG00000232045, ENSG00000236759 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000013787 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Milner CM, Campbell RD (March 1993). "The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats". The Biochemical Journal. 290 (Pt 3): 811–8. doi:10.1042/bj2900811. PMC 1132354. PMID 8457211.
  6. ^ Tachibana M, Sugimoto K, Fukushima T, Shinkai Y (July 2001). "Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3". The Journal of Biological Chemistry. 276 (27): 25309–17. doi:10.1074/jbc.M101914200. PMID 11316813.
  7. ^ a b "Entrez Gene: EHMT2 euchromatic histone-lysine N-methyltransferase 2".
  8. ^ a b Nestler EJ (August 2015). Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms. International Review of Neurobiology. Vol. 124. pp. 151–70. doi:10.1016/bs.irn.2015.07.003. ISBN 9780128015834. PMC 4690450. PMID 26472529.
  9. ^ a b "Histone-lysine N-methyltransferase, H3 lysine-9 specific 3". HIstome: The Histone Infobase. Retrieved 8 June 2018.
  10. ^ "Histone-lysine N-methyltransferase, H3 lysine-9 specific 5". HIstome: The Histone Infobase. Retrieved 8 June 2018.
  11. ^ a b c d Nestler EJ (January 2014). "Epigenetic mechanisms of drug addiction". Neuropharmacology. 76 (Pt B): 259–68. doi:10.1016/j.neuropharm.2013.04.004. PMC 3766384. PMID 23643695.
  12. ^ Whalley K (December 2014). "Psychiatric disorders: a feat of epigenetic engineering". Nature Reviews. Neuroscience. 15 (12): 768–9. doi:10.1038/nrn3869. PMID 25409693. S2CID 11513288.
  13. ^ Robison AJ, Nestler EJ (October 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
    Figure 4: Epigenetic basis of drug regulation of gene expression
  14. ^ a b Laumet, Geoffroy (2015). "G9a is essential for epigenetic silencing of K+ channel genes in acute-to-chronic pain transition". Nature Neuroscience. 18 (12): 1746–1755. doi:10.1038/nn.4165. PMC 4661086. PMID 26551542.
  15. ^ Liang, Lingli (2016). "G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons". Scientific Reports. 6: 37704. Bibcode:2016NatSR...637704L. doi:10.1038/srep37704. PMC 5118693. PMID 27874088.
  16. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  17. ^ Dutta A, et al. (June 2016). "Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation". Science. 352 (6293): 1576–80. Bibcode:2016Sci...352.1576D. doi:10.1126/science.aad9512. PMC 5507586. PMID 27339988.

Further readingEdit