hypomethylation

Hypomethylation refers to a reduction in DNA methylation, typically the loss of 5-methylcytosine (5mC) at CpG sites. It can be genome-wide or at specific loci. DNA methylation is a key epigenetic modification involved in regulating gene expression, maintaining genome stability, and enabling normal development.

Hypomethylation arises from decreased DNA methyltransferase activity (DNMT1, DNMT3A/3B), errors in maintenance methylation, or active demethylation via TET-mediated oxidation (5mC to 5hmC and further) followed by base excision repair. It can also reflect passive loss during replication in rapidly dividing cells when maintenance methylation is incomplete. Environmental factors and aging can influence methylation levels.

Genome-wide hypomethylation often affects repetitive elements, leading to genomic instability, chromosomal rearrangements, and activation of transposable elements. Locus-specific hypomethylation, including promoter regions, can activate oncogenes or disrupt imprinting. Hypomethylation is prominent in embryonic development and germline reprogramming, occurs transiently in early embryos, and is often present in cancer as part of broader epigenetic dysregulation.

Techniques include bisulfite sequencing, methylation arrays, and pyrosequencing, which quantify 5mC at CpGs. Interpretation requires genomic context, as loss of methylation in repetitive regions has different implications than promoter hypomethylation. Therapeutic or diagnostic implications are under investigation; methylation patterns serve as biomarkers in oncology and developmental studies.