DNMT3A

DNA (cytosine-5)-methyltransferase 3A is an is_associated_with::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 is_associated_with::gene.

Function
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.

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

Interactions
DNMT3A has been shown to interact with:


 * is_associated_with::DNMT1,
 * is_associated_with::DNMT3B,
 * is_associated_with::HDAC1,
 * is_associated_with::Myc,
 * is_associated_with::PIAS1,
 * PIAS2,
 * is_associated_with::SUV39H1,
 * is_associated_with::UBE2I and
 * is_associated_with::ZNF238.

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

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