CpG sites, epigenetic marks, gene regulation

DNA methylation

DNA methylation is an epigenetic modification in which methyl groups are added to DNA bases. In many eukaryotes, methylation at CpG sites helps regulate gene activity, genome stability, development, and cell identity.

Basic idea
DNA methylation adds methyl groups to DNA without changing the base sequence.
Common site
In mammals, DNA methylation often occurs at cytosines in CpG dinucleotides.
Gene regulation
Methylation near regulatory regions can influence whether nearby genes are active or quiet.
DNA methylation and demethylation change chemical marks at CpG sites without changing the underlying DNA sequence.View image on Wikimedia Commons

What DNA methylation is

DNA methylation is a chemical modification of DNA. A methyl group is added to a base, most often cytosine in CpG sites in mammalian genomes. The DNA sequence still reads the same in ordinary A, C, G, and T letters, but the marked base can change how proteins interact with that region.

CpG sites and CpG islands

A CpG site is a cytosine followed by a guanine along the same DNA strand. CpG islands are regions with many CpG sites and are often found near gene promoters. When promoter-associated CpG islands become methylated, transcription can be reduced, although the effect depends on context.

How methylation affects genes

DNA methylation can help repress transcription by changing protein binding or by recruiting proteins that compact chromatin. It is one layer of gene regulation, not a single master switch. The same mark can have different meanings depending on whether it lies in a promoter, gene body, enhancer, repeat, or other region.

Writing and erasing marks

Cells use DNA methyltransferases to add methyl groups and several pathways to remove or dilute methylation. Maintenance methylation can copy patterns after DNA replication, while active and passive demethylation can reshape those patterns during development, differentiation, and cellular responses.

Development and imprinting

DNA methylation is important during development because cells must establish and maintain different regulatory programs. It also participates in genomic imprinting, where some genes are expressed differently depending on whether they came from the mother or father. These patterns are carefully controlled and can be reset in particular stages of reproduction and development.

Genome stability

Methylation is also linked to genome defense. Repetitive sequences and transposable elements are often methylated, which can help keep them inactive. When methylation patterns are disrupted, repeats may become more active and genome regulation can become less stable.

Measuring methylation

Researchers measure DNA methylation with methods such as bisulfite sequencing, methylation arrays, enrichment-based assays, and long-read approaches. Each method has tradeoffs in resolution, cost, coverage, and ability to distinguish related chemical forms, so experimental design matters.

Why it matters

DNA methylation helps connect genome sequence to cell behavior. It is studied in development, cancer, aging, neuroscience, environmental biology, and epigenetic clocks. Its importance also demands caution: a methylation difference may be a cause, a consequence, or a marker of another process.