demetylaation

Demethylation (sometimes rendered as demetylation) is the chemical process of removing methyl groups from molecules. The term applies to both chemical synthesis and biological systems, where methyl marks on DNA or proteins influence gene expression and chromatin structure.

In organic chemistry, demethylation describes the removal of methyl substituents from heteroatoms or carbon centers. Common targets include O- and N-methyl groups. Reactions use reagents such as boron tribromide, hydrogen halides, or catalytic hydrogenolysis, and the method chosen depends on substrate sensitivity and the desired site of cleavage.

In biology, DNA demethylation entails removing methyl groups from 5-methylcytosine; TET enzymes oxidize to 5-hydroxymethylcytosine and further to 5-formyl and 5-carboxyl cytosine, followed by base excision repair to restore cytosine. Histone demethylation removes methyl groups from lysine (and sometimes arginine) residues on histone tails; mechanisms include Fe(II)/α-ketoglutarate–dependent JmjC-domain demethylases and the FAD-dependent LSD1 family, which together regulate chromatin structure and gene expression.

Demethylation plays roles in development, imprinting, and cellular differentiation; dysregulation is associated with cancer and other diseases. Understanding demethylation mechanisms informs epigenetic therapies and synthetic chemistry approaches.