DNA methyltransferase 1
The DNMT1 gene provides instructions for making an enzyme called DNA methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.
DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to migrate where needed and connect with each other, and neuron survival.
At least six DNMT1 gene mutations have been identified in people with hereditary sensory and autonomic neuropathy type IE (HSAN IE), a disorder characterized by a gradual loss of intellectual function (dementia), hearing loss, and sensory problems in the feet. Most of the mutations are in a region of the gene called exon 20, and reduce or eliminate the DNA methyltransferase 1 enzyme's methylation function. As a result, maintenance of the neurons that make up the nervous system is impaired. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE.
Several normal variations (polymorphisms) in the DNMT1 gene have been associated with an increased risk of cancer, including cancers of the breast and stomach. These variations, which are found in cells throughout the body and can be passed on from parent to child, may affect the activity of the DNA methyltransferase 1 enzyme and its role in gene silencing. Changes in the silencing of particular genes can lead to abnormal cell growth and division and increase the risk of cancer.
In addition, increased activity (overexpression) of the DNMT1 gene has been identified in certain brain cancers called gliomas. The genetic changes involved in this overexpression are somatic, which means that they occur only in the tumor cells and are not inherited. Researchers suggest that overexpression of the DNMT1 gene may result in methylation and silencing of genes called tumor suppressors. When tumor suppressor genes are silenced, cells can grow and divide unchecked, which can lead to cancer.
At least four DNMT1 gene mutations have been identified in people with another nervous system disorder called autosomal dominant cerebellar ataxia, deafness, and narcolepsy. Features of this disorder include difficulty coordinating movements (ataxia), hearing loss, and excessive daytime sleepiness (narcolepsy). Most of the mutations associated with this disorder are in a region of the DNMT1 gene known as exon 21, while mutations associated with HSAN IE (described above) are more often found in exon 20. Mutations in different locations within the gene may affect the DNA methyltransferase 1 enzyme differently, which can lead to particular combinations of signs and symptoms.
- CXXC finger protein 9
- CXXC-type zinc finger protein 9
- DNA (cytosine-5-)-methyltransferase 1
- DNA (cytosine-5)-methyltransferase 1
- DNA methyltransferase HsaI
- DNA MTase HsaI