DNA methylation at CpG islands
Imagine you could stamp a small 'do not read' seal directly onto certain pages of a book, in a way that survives photocopying. The cell can do something like this to its DNA: it can attach a tiny chemical tag, a methyl group, onto particular bases, and where these tags cluster densely over a gene's start, that gene tends to fall silent. This is DNA methylation, the most stable and best understood epigenetic mark in mammals.
The tag goes onto cytosine, one of the four DNA bases, turning it into 5-methylcytosine — chemically still a cytosine, still pairing with guanine, but now carrying a small methyl bump in the major groove. In mammals it happens almost only where a cytosine is immediately followed by a guanine on the same strand, a spot written 'CpG' (the p just means the phosphate linking them). Because C-pairs-with-G and G-pairs-with-C, a CpG on one strand sits across from a CpG on the other, so the pattern is symmetric — and that symmetry is the trick for heredity: after DNA copies, a maintenance enzyme reads the methyl tag on the old strand and copies it onto the matching CpG of the new strand, so the pattern persists through cell division. Many gene promoters sit in CpG islands, short regions unusually rich in CpG sites; these islands are normally kept unmethylated and the gene stays available, but when an island becomes methylated, reader proteins and compacting machinery move in and the gene is locked off.
DNA methylation matters wherever a gene must be shut durably: it silences one copy of imprinted genes, helps shut down one X chromosome in females, and keeps transposable elements and viral remnants permanently muzzled. Its failures are central to disease — in cancer, tumor-suppressor genes are frequently silenced by aberrant methylation of their CpG islands while the rest of the genome loses methylation, and several approved cancer drugs work by stripping these marks off. An honest caveat: methylation usually accompanies and reinforces silencing rather than being the lone first cause, and in some genomic locations (gene bodies, certain tissues) methylation correlates with activity, not silence — context decides.
In many colon cancers the CpG island in front of the repair gene MLH1 becomes heavily methylated, switching the gene off; the cell then loses its mismatch-repair ability and accumulates mutations — a silencing caused by a chemical mark, not by any change in the gene's letters.
A methyl tag on cytosine — symmetric across the strands, so it survives DNA copying.
Methylation is not always silencing. In gene bodies it often goes with active transcription, and not every silent gene is methylated. The reliable rule is narrower: heavy methylation of a CpG island over a promoter tends to shut that gene.