DNAmetylation

DNAmetylation, or DNA methylation, is an epigenetic modification in which a methyl group is added to the 5-position of cytosine residues in DNA, most often at CpG dinucleotides in animals. This chemical mark can regulate gene expression without changing the DNA sequence and can be propagated through cell divisions, contributing to developmental programs and cellular identity.

Enzymes called DNA methyltransferases install methylation. DNMT1 maintains methylation patterns during DNA replication by copying the parental marks to the new strand. De novo methyltransferases DNMT3A and DNMT3B establish new methylation marks in specific genomic contexts, with DNMT3L acting as a regulatory cofactor. In plants, methylation also occurs at non-CpG contexts (CHG, CHH).

Functionally, promoter methylation in CpG islands is usually associated with transcriptional repression, while methylation within gene bodies can correlate with active transcription in some genes. Methylation also helps suppress transposable elements and participates in imprinting and X-chromosome inactivation. The distribution of methylation is tissue-specific and changes during development and aging.

DNA methylation is dynamic. Active demethylation involves TET enzymes that oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives, followed by base excision repair. Passive demethylation can occur when maintenance methylation is reduced during replication.

Clinical and research relevance includes associations with cancer and developmental disorders, where aberrant methylation of promoters or global hypomethylation can disrupt gene regulation. Methods to study methylation include bisulfite sequencing and methylation arrays. Therapeutic DNMT inhibitors, such as azacitidine and decitabine, are used in certain myeloid malignancies and research settings to reverse abnormal methylation.