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DNA (cytosine-5-)-methyltransferase 3 alpha
Protein DNMT3A PDB 2QRV.png
Rendering based on PDB 2QRV.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM602769 MGI1261827 HomoloGene7294 IUPHAR: 2750 ChEMBL: 1992 GeneCards: DNMT3A Gene
EC number
RNA expression pattern
PBB GE DNMT3A 218457 s at tn.png
More reference expression data
Species Human Mouse
Entrez 1788 13435
Ensembl ENSG00000119772 ENSMUSG00000020661
UniProt Q9Y6K1 O88508
RefSeq (mRNA) NM_022552 NM_001271753
RefSeq (protein) NP_072046 NP_001258682
Location (UCSC) Chr 2:
25.46 – 25.57 Mb
Chr 12:
3.81 – 3.91 Mb
PubMed search [1] [2]

DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.[1][2]


CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than the maintenance of existing methylated sites. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms.[3]

Clinical relevance[edit]

The study of this gene in mice has shown its reduced expression in ageing animals causes cognitive long-term memory decline.[4] It is also frequently mutated in cancer, being one of 127 frequently mutated genes identified in the Cancer Genome Atlas project, in a publication involving whole-genome sequencing on 3,281 cancers of various types.[5] In the Cancer Genome Atlas study, DNMT3A mutations were most commonly seen in acute myeloid leukaemia where they occurred in just over 25% of cases sequenced. Mutations were also relatively common in lung cancers.


DNMT3A has been shown to interact with:

Model organisms[edit]

Model organisms have been used in the study of DNMT3A function. A conditional knockout mouse line called Dnmt3atm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[12] Male and female animals underwent a standardized phenotypic screen[13] to determine the effects of deletion.[14][15][16][17] Additional screens performed: - In-depth immunological phenotyping[18]


  1. ^ Okano M, Xie S, Li E (1998). "Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases". Nat. Genet. 19 (3): 219–20. doi:10.1038/890. PMID 9662389. 
  2. ^ Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW et al. (1999). "Cloning, expression and chromosome locations of the human DNMT3 gene family". Gene 236 (1): 87–95. doi:10.1016/S0378-1119(99)00252-8. PMID 10433969. 
  3. ^ "Entrez Gene: DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha". 
  4. ^ Oliveira AM, Hemstedt TJ, Bading H (2012). "Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities". Nat. Neurosci. 15 (8): 1111–3. doi:10.1038/nn.3151. PMID 22751036. 
  5. ^ Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C et al. (2013). "Mutational landscape and significance across 12 major cancer types". Nature 502 (7471): 333–9. doi:10.1038/nature12634. PMID 24132290. 
  6. ^ a b Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". EMBO J. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218. 
  7. ^ a b c d Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD (2004). "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048. 
  8. ^ Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S et al. (2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Curr. Biol. 13 (14): 1192–200. doi:10.1016/s0960-9822(03)00432-9. PMID 12867029. 
  9. ^ a b Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (2001). "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription". EMBO J. 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943. 
  10. ^ Brenner C, Deplus R, Didelot C, Loriot A, Viré E, De Smet C et al. (2005). "Myc represses transcription through recruitment of DNA methyltransferase corepressor". EMBO J. 24 (2): 336–46. doi:10.1038/sj.emboj.7600509. PMC 545804. PMID 15616584. 
  11. ^ Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003). "The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase". Nucleic Acids Res. 31 (9): 2305–12. doi:10.1093/nar/gkg332. PMC 154218. PMID 12711675. 
  12. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley. 
  13. ^ a b "International Mouse Phenotyping Consortium". 
  14. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  15. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  16. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  17. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMID 23870131. 
  18. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium". 

Further reading[edit]