DNAmetylaation

DNA methylation, sometimes spelled DNAmetylaation, is a biochemical modification in which a methyl group is added to DNA, most commonly at the 5-carbon of cytosine to form 5-methylcytosine. In animals, this occurs mainly at CpG dinucleotides, though non-CpG methylation exists in certain cells and broader contexts are observed in plants. Methylation patterns are established during development and maintained through cell divisions, contributing to cellular identity and genome stability.

Enzymes and contexts: DNA methyltransferases (DNMTs) catalyze methylation. DNMT1 maintains methylation after DNA replication; DNMT3A and DNMT3B establish new methylation (de novo). DNMT3L is a regulatory factor without catalytic activity. In plants, methylation also occurs in CHG and CHH contexts, expanding the possible sequence targets.

Biological roles: methylation of promoter regions is often associated with gene silencing, while methylation of transposable elements helps suppress their activity. Imprinting, X-chromosome inactivation, development, and aging are linked to DNA methylation patterns. Abnormal methylation is a feature of many cancers and other diseases, making methylation a focus of diagnostics and research.

Mechanisms: methylated DNA can hinder transcription factor binding and recruit methyl-CpG-binding domain proteins that attract repressive chromatin modifiers. Demethylation occurs through TET enzymes that oxidize 5mC to 5-hydroxymethylcytosine and further derivatives, followed by repair processes; both active and passive demethylation contribute to dynamic regulation.

Detection and study: researchers use bisulfite sequencing (genome-wide or targeted), methylation arrays, and methods like reduced representation bisulfite sequencing to map methylation, while accounting for tissue specificity and cellular heterogeneity.