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DNMT3A (DNA methyltransferase 3 alpha)

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Summary of DNMT3A

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 (R).

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The Function of DNMT3A

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity.

Protein names

Recommended name:

DNA

Alternative name(s):

cytosine-5
Dnmt3a
DNA methyltransferase HsaIIIA
DNA MTase HsaIIIA
M.HsaIIIA

DNMT3A SNPs

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

  1. RS11694842 (DNMT3A) ??
  2. RS11695471 (DNMT3A) ??
  3. RS11887120 (DNMT3A) ??
  4. RS13428812 (DNMT3A) ??
  5. RS141216273 (DNMT3A) ??
  6. RS2289195 (DNMT3A) ??
  7. RS6722613 (DNMT3A) ??

Top Gene-Substance Interactions

DNMT3A Interacts with These Diseases

Disease Score

Substances That Increase DNMT3A

Substances Interaction Organism Category

Substances That Decrease DNMT3A

Substances Interaction Organism Category

Advanced Summary

     cytogenetically normal acute myeloid leukemia Mutations in the DNMT3A gene are associated with a form of blood cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML. Up to one-third of people with CN-AML have a mutation in the DNMT3A gene. The DNMT3A gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. Most change single protein building blocks (amino acids) in the DNA methyltransferase 3 alpha enzyme. Studies suggest that these changes make the enzyme less able to fully methylate DNA. It is also thought that the altered pattern of methylation in cells changes the activity of several genes; some genes that are normally silenced may be turned on. Researchers speculate that the altered gene activity prevents hematopoietic stem cells from differentiating normally, which leads to the overproduction of abnormal, immature white blood cells characteristic of acute myeloid leukemia. other cancers Somatic DNMT3A gene mutations are also found relatively frequently in another form of blood cancer called T-cell acute lymphoblastic leukemia. As in CN-AML, the mutations disrupt the normal pattern of methylation in cells, which blocks differentiation. It is unclear why some people with DNMT3A gene mutations develop acute myeloid leukemia and others develop acute lymphoblastic leukemia.

     The DNMT3A gene provides instructions for making an enzyme called DNA methyltransferase 3 alpha. 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 3 alpha is particularly important for establishing the initial locations for methylation during development. The enzyme also functions in early cells that can give rise to more mature cell types. In early blood cells, called hematopoietic stem cells, the methylation patterns established by DNA methyltransferase 3 alpha promote maturation (differentiation) into different blood cell types.

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:

  • ER-alpha
  • p53
  • Meis-1
  • Meis-1b

Tissue specificity:

Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung.

Gene Pathways:

  • Metabolic pathways
  • Gene Expression
  • Chromatin organization
  • Cysteine and methionine metabolism

Caution:

It is uncertain whether Met-1 or Met-4 is the initiator.

Enzyme Regulation:

Activated by binding to the regulatory factor DNMT3L.

Molecular Function:

  • Chromatin Binding
  • Dna (Cytosine-5-)-Methyltransferase Activity
  • Dna (Cytosine-5-)-Methyltransferase Activity, Acting On Cpg Substrates
  • Dna Binding
  • Dna-Methyltransferase Activity
  • Identical Protein Binding
  • Metal Ion Binding
  • Unmethylated Cpg Binding

Biological Processes:

  • Aging
  • Cellular Response To Amino Acid Stimulus
  • Cellular Response To Ethanol
  • Cellular Response To Hypoxia
  • Dna Methylation
  • Dna Methylation Involved In Embryo Development
  • Dna Methylation Involved In Gamete Generation
  • Dna Methylation On Cytosine Within A Cg Sequence
  • Hepatocyte Apoptotic Process
  • Methylation-Dependent Chromatin Silencing
  • Mitotic Cell Cycle
  • Negative Regulation Of Gene Expression, Epigenetic
  • Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Neuron Differentiation
  • Positive Regulation Of Cell Death
  • Regulation Of Gene Expression By Genetic Imprinting
  • Response To Cocaine
  • Response To Estradiol
  • Response To Ionizing Radiation
  • Response To Lead Ion
  • Response To Toxic Substance
  • Response To Vitamin A
  • S-Adenosylhomocysteine Metabolic Process
  • S-Adenosylmethioninamine Metabolic Process
  • Spermatogenesis
  • Hypermethylation Of Cpg Island
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_02240| D623_10031232| DNA (cytosine-5)-methyltransferase 3A| DNA (cytosine-5)-methyltransferase 3A-like| DNA (cytosine-5-)-methyltransferase 3 alpha| DNA cytosine methyltransferase 3A2| DNA cytosine methyltransferase 3 alpha| DNA methyltransferase 3a| DNA-methyltransferase 3a| DNA methyltransferase 3A-like 2 protein| DNA methyl transferase alpha| DNA methyltransferase MmuIIIA| DNA MTase HsaIIIA| DNA MTase MmuIIIA| DNMT3A2| I79_002537| M91_00138| M.HsaIIIA| MmuIIIA| N300_08359| N302_05438| N333_05938| PAL_GLEAN10020220| TBRS| UY3_09862| Y1Q_024238| Y956_16372| dnmt3a

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