Target intelligence / Profile preview

DNA methylation cycle

Molecular classification
Other (process), Enzyme (for core components: DNMTs, TETs)
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Overview

The DNA methylation cycle encompasses the reversible addition and removal of methyl groups to cytosine (and sometimes adenine) bases in DNA, predominantly at CpG sites, regulated by specific enzymes. DNA methylation typically represses gene transcription, especially when present at promoter regions. The cycle is regulated by DNA methyltransferases (DNMT1, DNMT3A, DNMT3B for methylation) and ten-eleven translocation (TET1, TET2, TET3 for demethylation) families, with cofactors such as S-adenosyl methionine (SAM). This process is central to normal development, cellular differentiation, genomic stability, and the suppression of repetitive elements. Alterations in methylation patterns are implicated in diverse diseases including cancers, aging-related diseases, and neurological disorders. Pharmacological targeting of the cycle's enzymes represents a strategy in cancer treatment, but broad manipulation of DNA methylation risks adverse, unpredictable long-term effects.

Other names
DNA methylation processDNA methylation/demethylation cycleepigenetic methylation cycle
02

Mechanism of action

Inhibition of DNA methyltransferases blocks the addition of methyl groups, leading to reactivation of silenced genes (e.g., tumor suppressor gene re-expression in cancer therapy) Modulation of TET proteins to influence active demethylation

03

Biological functions

Regulation of gene expressionEpigenetic programmingGenomic imprintingX-chromosome inactivationSuppression of transposable elementsDevelopment and differentiationResponse to environmental signals
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Disease associations

Cancer (aberrant methylation silences tumor suppressor genes)Aging (systematic methylation changes over lifespan)Neurological disease (epigenetic dysregulation)Developmental disordersOther (including metabolic and autoimmune conditions)
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Safety considerations

Off-target gene activation or silencingGenomic instabilityBone marrow suppression (from DNMT inhibitors)Potential carcinogenesis from aberrant demethylation
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Interacting drugs

Drugs that inhibit DNA methyltransferases (DNMTs), such as azacitidine and decitabine, target components of this cycle in cancer therapy
07

Biomarkers

5-methylcytosine (5mC) levelsPromoter methylation status of genes (e.g., MGMT in glioma, hMLH1 in colon cancer)Global DNA methylation profiles (epigenetic clocks for biological aging)

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