demethylations

Demethylation refers to the removal of methyl groups from substrates, and it occurs in both chemistry and biology. In chemistry, demethylation reactions remove methyl substituents from substrates such as amines, ethers, and alcohols, typically by oxidation, hydrolysis, or reductive cleavage. In biology, demethylation often describes changes in the methylation status of nucleic acids and histones that influence gene expression and chromatin structure.

Chemical demethylation methods include oxidative or hydrolytic processes that cleave N- or O-methyl groups, as well as reductive methods used for methyl ethers. Many reactions require specific catalysts or reagents and can differ in selectivity, substrate scope, and conditions. In practice, demethylation is used to reveal functional groups or to modify chemical reactivity and properties of molecules.

DNA demethylation in eukaryotes commonly refers to removing 5-methylcytosine from CpG sites. Passive demethylation occurs during DNA replication when maintenance methylation is incomplete. Active demethylation involves enzymatic pathways in which TET family dioxygenases oxidize 5mC to 5-hydroxymethylcytosine, then to 5-formylcytosine and 5-carboxylcytosine, which are replaced by unmethylated cytosine through base excision repair.

Histone demethylation is carried out by histone demethylases such as LSD1/KDM1A and JmjC-domain enzymes. These enzymes remove methyl groups from lysine residues on histone tails, often using cofactors like flavin adenine dinucleotide or α-ketoglutarate and iron. Demethylation of histones contributes to dynamic regulation of chromatin accessibility and transcription, with important roles in development and disease.