demethylate

Demethylate is a verb describing the removal of one or more methyl groups (–CH3) from a molecule. Demethylation can occur through chemical reactions in the laboratory or through enzymatic processes in living systems. The related noun is demethylation, and the term is commonly used across chemistry, biochemistry, and molecular biology.

In biology and biochemistry, demethylation plays a key role in regulating gene expression and chromatin structure. DNA demethylation refers to the removal of methyl groups from cytosine residues, which can lead to changes in transcriptional activity. In many organisms, active DNA demethylation involves TET family enzymes that oxidize 5-methylcytosine to derivatives that are then cleared and replaced, contributing to epigenetic remodeling. Histone demethylases remove methyl marks from histone tails, influencing chromatin accessibility and gene regulation. Two major classes are the FAD-dependent LSD1/LSD2 family and the Fe(II)/α-ketoglutarate–dependent JmjC-domain demethylases; these enzymes use oxidation chemistry to remove methyl groups from lysine residues and other histone marks.

In chemical contexts, demethylation refers to reactions that strip methyl groups from substrates, such as converting methyl ethers to phenols or removing N-methyl groups from amines. Common laboratory methods for demethylating methyl ethers include reagents like boron tribromide (BBr3) or Lewis/Brønsted acids that cleave the C–O–CH3 bond. Demethylation is also a strategy in organic synthesis to reveal functional groups or to modify protective groups.

Overall, demethylation encompasses both biological regulatory mechanisms and practical chemical transformations that remove methyl groups from diverse substrates.