At least three DNMT1 gene mutations have been identified in people with hereditary sensory and autonomic neuropathy (HSAN IE), a disorder characterized by a gradual loss of intellectual functions (dementia), deafness, and sensory problems in the feet. The mutations, which are in a region of the gene called exon 20, 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. cancers 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 can be passed on from parent to child, may affect the activity of the DNA methyltransferase 1 enzyme and the way it regulates other genes. Changes in the regulation of these 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. other disorders At least three 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). The mutations associated with this disorder are in a region of the DNMT1 gene known as exon 21, distinct from the mutations that cause HSAN IE (described above) which are 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.

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 (methylation), 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.

The following transcription factors affect gene expression:

• NF-kappaB
• p53
• STAT3
• NF-kappaB1
• Sp1
• AML1a
• p300

Tissue specificity:

Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1.

Induction:

Its abundance is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle.

Molecular Function:

• Dna Binding
• Double-Stranded Dna Binding
• Rna Binding
• Dna (Cytosine-5-)-Methyltransferase Activity
• Zinc Ion Binding
• Methyl-Cpg Binding
• Dna-Methyltransferase Activity
• Unmethylated Cpg Binding
• Dna (Cytosine-5-)-Methyltransferase Activity, Acting On Cpg Substrates
• Promoter-Specific Chromatin Binding

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Dna Methylation
• Transcription, Dna-Templated
• Ras Protein Signal Transduction
• Brain Development
• Aging
• Response To Heat
• Response To Toxic Substance
• Response To Ionizing Radiation
• Maintenance Of Dna Methylation
• Dna Methylation On Cytosine Within A Cg Sequence
• Positive Regulation Of Gene Expression
• Gene Silencing
• Covalent Chromatin Modification
• Neuron Differentiation
• Response To Caffeine
• Response To Estradiol
• Response To Lipopolysaccharide
• Response To Vitamin A
• Response To Testosterone
• Cellular Response To Platelet-Derived Growth Factor Stimulus
• Regulation Of Cell Proliferation
• Dna Methylation Involved In Embryo Development
• Dna Hypermethylation
• Response To Ethanol
• Negative Regulation Of Gene Expression, Epigenetic
• S-Adenosylhomocysteine Metabolic Process
• S-Adenosylmethioninamine Metabolic Process
• S-Adenosylmethionine Metabolic Process
• Positive Regulation Of Histone H3-K4 Methylation
• Negative Regulation Of Histone H3-K9 Methylation
• Cellular Response To Amino Acid Stimulus
• Cellular Response To Lead Ion
• Cellular Response To Transforming Growth Factor Beta Stimulus
• Positive Regulation Of Methylation-Dependent Chromatin Silencing
• Cellular Response To Nerve Growth Factor Stimulus

Drug Bank:

• Decitabine
• Procainamide
• Azacitidine
• Flucytosine