DNA Methylation

DNA methylation involves covalent attachment of methyl groups to cytosine bases predominantly within CpG dinucleotides establishing epigenetic modifications regulating gene silencing without altering nucleotide sequences. Aberrant methylation patterns characterise cancer, neurodegenerative diseases, and autoimmune conditions with therapeutic targeting increasingly addressing dysregulated methylation. Hypermethylation silences tumour suppressor genes promoting malignant transformation; conversely, hypomethylation of oncogene regulatory regions activates proto-oncogenes. Diagnostic applications assess methylation biomarkers predicting treatment response and prognosis across disease indications.

DNA methyltransferase inhibitors including azacitidine reverse aberrant methylation restoring silenced gene expression. Mechanisms involve covalent enzyme inactivation during nucleotide incorporation forcing methyltransferase-DNA covalent complex formation during replication. Clinical efficacy in myelodysplastic syndromes and acute myeloid leukaemia demonstrates methylation targeting utility. Emerging therapies combine methyltransferase inhibition with histone deacetylase inhibitors synergistically targeting epigenetic dysregulation. Regulatory approval of epigenetic modifiers increasingly recognises DNA methylation targeting as legitimate therapeutic strategy.