Page last updated: 2024-10-24
DNA demethylation
Definition
Target type: biologicalprocess
The removal of a methyl group from one or more nucleotides within an DNA molecule. [PMID:17208187]
DNA demethylation is a crucial biological process that involves the removal of methyl groups from DNA. It plays a vital role in gene regulation, cellular differentiation, and development. The removal of methyl groups alters the accessibility of DNA to transcription factors, influencing the expression of specific genes.
There are two primary pathways involved in DNA demethylation:
1. **Ten-eleven translocation (TET) enzyme-mediated oxidation:** This pathway involves a family of enzymes called TET enzymes, which catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). This process is further catalyzed by TET enzymes, leading to the formation of 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These oxidized forms of 5mC are then recognized and removed by thymine DNA glycosylase (TDG), initiating the base excision repair (BER) pathway, which ultimately results in the replacement of the modified cytosine with an unmodified cytosine.
2. **Active demethylation:** This pathway is primarily mediated by the enzyme thymine DNA glycosylase (TDG), which directly removes 5fC and 5caC from DNA. TDG recognizes these oxidized forms of 5mC as damaged bases and initiates the BER pathway, leading to the removal of the modified cytosine.
These two pathways work together to maintain the dynamic balance of DNA methylation patterns in the genome. DNA demethylation is essential for various cellular processes, including:
* **Gene expression:** Demethylation can activate gene expression by making DNA more accessible to transcription factors.
* **Cellular differentiation:** Demethylation plays a crucial role in the differentiation of stem cells into specialized cell types.
* **Development:** Demethylation is essential for normal embryonic development and organogenesis.
* **Immune response:** Demethylation is involved in the activation of immune cells and the regulation of immune responses.
Dysregulation of DNA demethylation is associated with various diseases, including cancer, autoimmune disorders, and neurodevelopmental disorders. Therefore, understanding the intricate mechanisms of DNA demethylation is crucial for developing therapeutic strategies to address these diseases.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Methylcytosine dioxygenase TET2 | A methylcytosine dioxygenase TET2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6N021] | Homo sapiens (human) |
| Single-stranded DNA cytosine deaminase | A single-stranded DNA cytosine deaminase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9GZX7] | Homo sapiens (human) |
Compounds (37)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| alpha-hydroxyglutarate | 2-hydroxyglutarate : A dicarboxylic acid anion obtained by deprotonation of at least one of the carboxy groups of 2-hydroxyglutaric acid. 2-hydroxyglutaric acid : A 2-hydroxydicarboxylic acid that is glutaric acid in which one hydrogen alpha- to a carboxylic acid group is substituted by a hydroxy group. | 2-hydroxydicarboxylic acid; dicarboxylic fatty acid | metabolite; mouse metabolite |
| hydroxylamine | amino alcohol : An alcohol containing an amino functional group in addition to the alcohol-defining hydroxy group. | hydroxylamines | algal metabolite; bacterial xenobiotic metabolite; EC 1.1.3.13 (alcohol oxidase) inhibitor; EC 4.2.1.22 (cystathionine beta-synthase) inhibitor; EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor; nitric oxide donor; nucleophilic reagent |
| aurintricarboxylic acid | aurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'. Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues. | monohydroxybenzoic acid; quinomethanes; tricarboxylic acid | fluorochrome; histological dye; insulin-like growth factor receptor 1 antagonist |
| chelerythrine | chelerythrine : A benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae. | benzophenanthridine alkaloid; organic cation | antibacterial agent; antineoplastic agent; EC 2.7.11.13 (protein kinase C) inhibitor |
| deferoxamine | Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator. | acyclic desferrioxamine | bacterial metabolite; ferroptosis inhibitor; iron chelator; siderophore |
| dequalinium | dequalinium : A quinolinium ion comprising decane in which one methyl hydrogen at each end of the molecule has been replaced by a 4-amino-2-methylquinolin-1-yl group. Dequalinium: A topical bacteriostat that is available as various salts. It is used in wound dressings and mouth infections and may also have antifungal action, but may cause skin ulceration. | quinolinium ion | antifungal agent; antineoplastic agent; antiseptic drug; mitochondrial NADH:ubiquinone reductase inhibitor |
| diphenyleneiodonium | dibenziodolium : An organic cation that is fluorene in which the methylene group is replaced by a positively charged iodine. diphenyleneiodonium: structure in first source; NADPH oxidase inhibitor | organic cation | |
| dipyridamole | dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots. Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752) | piperidines; pyrimidopyrimidine; tertiary amino compound; tetrol | adenosine phosphodiesterase inhibitor; EC 3.5.4.4 (adenosine deaminase) inhibitor; platelet aggregation inhibitor; vasodilator agent |
| 2,3-dimethoxy-1,4-naphthoquinone | 2,3-dimethoxynaphthalene-1,4-dione : A naphthoquinone that is 1,4-naphthoquinone bearing two methoxy substituents at positions 2 and 3. Redox-cycling agent that induces intracellular superoxide anion formation and, depending on the concentration, induces cell proliferation, apoptosis or necrosis. Used to study the role of ROS in cell toxicity, apoptosis, and necrosis. | 1,4-naphthoquinones | |
| hydralazine | hydralazine : The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent. Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. | azaarene; hydrazines; ortho-fused heteroarene; phthalazines | antihypertensive agent; vasodilator agent |
| phenelzine | Phenelzine: One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC. | primary amine | |
| beta-lapachone | beta-lapachone : A benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities. beta-lapachone: antineoplastic inhibitor of reverse transcriptase, DNA topoisomerase, and DNA polymerase | benzochromenone; orthoquinones | anti-inflammatory agent; antineoplastic agent; plant metabolite |
| mitoxantrone | mitoxantrone : A dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8. Mitoxantrone: An anthracenedione-derived antineoplastic agent. | dihydroxyanthraquinone | analgesic; antineoplastic agent |
| protoporphyrin ix | protoporphyrin : A cyclic tetrapyrrole that consists of porphyrin bearing four methyl substituents at positions 3, 8, 13 and 17, two vinyl substituents at positions 7 and 12 and two 2-carboxyethyl substituents at positions 2 and 18. The parent of the class of protoporphyrins. protoporphyrin IX: RN given refers to parent cpd; structure in Merck Index, 9th ed, #7685 | ||
| sanguinarine | benzophenanthridine alkaloid : A specific group of isoquinoline alkaloids that occur only in higher plants and are constituents mainly of the Papaveraceae family. | alkaloid antibiotic; benzophenanthridine alkaloid; botanical anti-fungal agent | |
| tyrphostin a9 | alkylbenzene | geroprotector | |
| 1-naphthaldehyde | 1-naphthaldehyde : A naphthaldehyde with a formyl group at position 1. 1-naphthaldehyde: structure naphthaldehyde : An aldehyde in which the organyl group is a naphthyl group. | naphthaldehyde | mouse metabolite |
| pyrazolanthrone | anthra[1,9-cd]pyrazol-6(2H)-one : A member of the class of anthrapyrazoles that is anthra[1,9-cd]pyrazole substituted at position 6 by an oxo group. An inhibitor of c-Jun N-terminal kinase. pyrazolanthrone: JNK (c-Jun N-terminal kinase) inhibitor; structure in first source | anthrapyrazole; aromatic ketone; cyclic ketone | antineoplastic agent; c-Jun N-terminal kinase inhibitor; geroprotector |
| 2,3,5-trimethylquinol | 2,3,5-trimethylhydroquinone : A member of the class of hydroquinones that is hydroquinone substituted by methyl groups at positions 2, 3 and 5. 2,3,5-trimethylquinol: reducing agent | hydroquinones; methylbenzene | |
| idarubicin | Idarubicin: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA. | anthracycline antibiotic; deoxy hexoside; monosaccharide derivative | |
| flupirtine | flupirtine: RN given refers to parent cpd without isomeric designation | aminopyridine | |
| masoprocol | masoprocol : The meso-form of nordihydroguaiaretic acid. An antioxidant found in the creosote bush, Larrea divaricata, it is a potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. It also inhibits (though to a lesser extent) formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase. Masoprocol: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. | nordihydroguaiaretic acid | antineoplastic agent; hypoglycemic agent; lipoxygenase inhibitor; metabolite |
| 2-(4-aminophenyl)quinoline | 2-(4-aminophenyl)quinoline: used for imaging tau protein; structure in first source | ||
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| IPA-3 | IPA-3 : An organic disulfide obtained by oxidative dimerisation of 1-sulfanylnaphthalen-2-ol. | naphthols; organic disulfide | EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor |
| 2-[[2-methyl-5-(3-methyl-4-oxo-1-phthalazinyl)phenyl]sulfonylamino]acetic acid ethyl ester | alpha-amino acid ester | ||
| (2'-(4-aminophenyl)-(2,5'-bi-1h-benzimidazol)-5-amine) | benzimidazoles | ||
| nemadipine-a | nemadipine-A : A dihydropyridine that is that is 1,4-dihydropyridine which is substituted at positions 2 and 6 by methyl groups, at positions 3 and 5 by ethoxycarbonyl groups, and at position 4 by a pentafluorophenyl group. An L-type calcium channel alpha1-subunit antagonist. When exposed to the microscopic soil nematode Caenorhabditis elegans, nemadipine-A induces a variety of defects including those affecting morphology and egg laying. nemadipine-A: structure in first source | dicarboxylic acids and O-substituted derivatives; diester; dihydropyridine; ethyl ester; pentafluorobenzenes | calcium channel blocker |
| 5-[[(1-cyclohexyl-5-tetrazolyl)thio]methyl]-3-phenyl-1,2,4-oxadiazole | oxadiazole; ring assembly | ||
| oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
| ro 41-0960 | |||
| tectochrysin | tectochrysin : A monohydroxyflavone that is flavone substituted by a hydroxy group at position 4 and a methoxy group at position 7 respectively. tectochrysin: structure in first source | monohydroxyflavone; monomethoxyflavone | antidiarrhoeal drug; antineoplastic agent; plant metabolite |
| casein kinase ii | Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression. | ||
| 2-(2-methoxyanilino)-8-[(3-methyl-1-piperidinyl)-oxomethyl]-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-one | N-acylpiperidine | ||
| CDN1163 | CDN1163 : A secondary carboxamide resulting from the formal condensation of the carboxy group of 4-isopropoxybenzoic acid with the primary amino group of 2-methylquinolin-8-amine. An allosteric activator of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA). CDN1163: a SERCA2 activator with antidiabetic activity; structure in first source | aromatic ether; quinolines; secondary carboxamide | SERCA activator |
| hispidin | hispidin : Fungal metabolite first found in basidiomycete Inonotus hispidus (formerly Polyporus hispidus). hispidin: metabolite of Basidiomycete Polyporus hispidus | 2-pyranones; catechols | antioxidant; EC 2.7.11.13 (protein kinase C) inhibitor; fungal metabolite |
| 4-[[(4-oxo-1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-2-yl)thio]methyl]benzoic acid methyl ester | benzoate ester |