epimutation

An epimutation is a heritable alteration in gene expression that arises from changes in the epigenetic state rather than a change in the DNA sequence. Epimutations can affect a single gene or regulatory regions and may be transmitted through cell divisions; some germline (constitutional) epimutations can be passed to offspring, while many are limited to somatic tissues.

Epimutations typically involve changes in DNA methylation at promoters or enhancers, but can also include alterations in histone modifications, chromatin structure, or non-coding RNA regulation that influence transcription. They may be stable across cell generations or, in other cases, show tissue-specific or reversible patterns.

Causes include spontaneous occurrence, environmental exposures, aging, or mutations in genes that control epigenetic marks (such as DNA methyltransferases, demethylases, or histone modifiers).

Examples in humans include constitutional MLH1 promoter methylation associated with Lynch syndrome and epimutations at imprinted loci that underlie certain imprinting disorders. Epimutations are also studied in cancer, where silencing of tumor suppressor genes by promoter methylation can contribute to tumor development.

Detection relies on assays for DNA methylation and chromatin state, such as bisulfite sequencing and methylation arrays; epigenome-wide association studies explore their disease associations. Therapeutically, reversal of some epimutations by epigenetic drugs is an area of research.

Epimutations illustrate how gene expression can be altered without changing DNA sequence, with implications for development, inheritance, and disease.