unmethylated

Unmethylated refers to the absence of a methyl group as a chemical modification on a molecule. In biology, the term is most commonly applied to DNA, where unmethylated cytosines—especially within CpG dinucleotides—lack a methyl group, in contrast to methylated cytosines.

In the context of DNA, methylation is a common epigenetic modification that can influence gene expression. Methylated promoter regions often correlate with reduced transcription, while unmethylated promoters, particularly those in CpG islands, are typically associated with active transcription and accessible chromatin. Methylation patterns are dynamic during development and can be altered in disease, with promoter hypermethylation contributing to gene silencing in cancer and other conditions.

The establishment and maintenance of DNA methylation involve DNA methyltransferases, including DNMT3A and DNMT3B for de novo methylation and DNMT1 for maintenance during DNA replication. Demethylation can occur passively through replication without maintenance methylation or actively via the TET enzyme-mediated oxidation of 5-methylcytosine, followed by repair processes that restore unmethylated cytosine.

Detection methods, such as bisulfite sequencing, distinguish unmethylated from methylated cytosines by chemical conversion, enabling genome-wide or targeted analyses of methylation status.

Outside DNA, unmethylated can describe RNA molecules lacking methyl modifications. RNA methylation, including N6-methyladenosine (m6A), influences splicing, stability, and translation; unmethylated transcripts may exhibit different regulatory behaviors, though RNA methylation patterns are complex and tissue-specific.

Overall, unmethylated status is a key feature in epigenetic regulation, signaling potential gene activity and chromatin accessibility, and it contrasts with methylated states that are often linked to repression or altered regulation.