DNA methylation

Meaning: DNA methyltransferases transfer a methyl group, donated by S-adenosylmethionine, to carbon 5 of cytosine, mostly where cytosine is followed by guanine (a CpG site). CpG-rich stretches near promoters are called CpG islands. When a promoter is methylated, methyl-binding proteins recruit complexes that deacetylate histones and condense chromatin, so transcription factors reach the gene less easily and expression usually falls. After replication, a maintenance methyltransferase methylates the new strand opposite the old methylated strand, so the pattern passes to daughter cells. X-inactivation and genomic imprinting rely on it.

On the MCAT: Passages typically give gene expression alongside methylation level, or treat cells with a demethylating agent. Predict that more promoter methylation means less transcription, and that removing methyl groups raises it. Hypermethylation of a tumor suppressor promoter is a common example. Bacteria also methylate their own DNA, which protects it from their restriction enzymes.

Common confusion: Methylation is not a mutation. The base sequence is unchanged and the mark is reversible. Do not mix it up with histone acetylation, which loosens chromatin and generally raises transcription. Histone methylation can activate or repress depending on the site, but methylation of promoter DNA typically represses.