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DNMT1 (DNA methyltransferase 1)

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Summary of DNMT1

This gene encodes an enzyme that is involved in DNA methylation . DNA methylation is needed for determining whether the instructions in a particular segment of DNA are carried out or suppressed, regulating reactions involving proteins and fats, and controlling the processing of chemicals. It is associated with cancer, deafness, narcolepsy, and other disorders (R).

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The Function of DNMT1

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306).

Protein names

Recommended name:

DNA

Short name:

MCMT

Alternative name(s):

cytosine-5
Dnmt1
CXXC-type zinc finger protein 9
DNA methyltransferase HsaI
DNA MTase HsaI
M.HsaI

DNMT1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS16999593 (DNMT1) ??
  2. RS2116940 (DNMT1) ??
  3. RS2228611 (DNMT1) ??
  4. RS2228612 (DNMT1) ??

Top Gene-Substance Interactions

DNMT1 Interacts with These Diseases

Disease Score

Substances That Increase DNMT1

Substances Interaction Organism Category

Substances That Decrease DNMT1

Substances Interaction Organism Category

Advanced Summary

     hereditary sensory and autonomic neuropathy type IE 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.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

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.

Gene Pathways:

  • Metabolic pathways
  • Gene Expression
  • Mus musculus biological processes
  • Cysteine and methionine metabolism

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

Biological Processes:

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

Drug Bank:

  • Decitabine
  • Procainamide
  • Azacitidine
  • Flucytosine
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| AIM| A306_12714| ADCADN| AS27_09985| BmDnmt1| Cxxc9| CXXC-type zinc finger protein 9| D623_10007965| ddn| dmnt1| DNA-C5-methyltransferase-1| DNA cytosine-5 methyltransferase| DNA (cytosine 5 ) methyltransferase 1| DNA (cytosine-5-)-methyltransferase 1| DNA (cytosine-5)-methyltransferase 1| DNA (cytosine-5)-methyltransferase 1-like protein| DNA MeTase| DNA methyltransferase 1-like protein| DNA methyltransferase b| DNA methyltransferase (cytosine-5) 1| DNA methyltransferase (cytosine 5 ) methyltransferase| DNA methyltransferase GgaI| DNA methyltransferase HsaI| DNA methyltransferase I| DNA methyltransferase MmuI| DNA MTase GgaI| DNA MTase HsaI| DNA MTase MmuI| DNA MTase RnoIP| DNMT| Dnmt1o| EH28_05210| Eukaryotic translation initiation factor 3 subunit G| fb05h01| HSN1E| I79_005894| mcmt| MDA_GLEAN10009309| Met1| Met-1| m.GgaI| m.HsaI| m.MmuI| MommeD2| m.RnoIP| mta| MTase| N301_05020| N303_13533| N306_06893| N308_04136| N309_13560| N320_04937| N327_03939| N329_11431| N333_08421| PAL_GLEAN10002439| PANDA_010327| Sphingosine 1-phosphate receptor 2| TREES_T100002065| xDnmt1| Y1Q_009819| Y956_11319| dnmt1

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