Histone H3 lysine 36 dimethylation (H3K36me2)

Histone H3 lysine 36 dimethylation (H3K36me2) is a covalent post-translational modification of the core histone H3 at lysine 36. It is installed by specific methyltransferases (notably NSD1, NSD2, ASH1L, SMYD2), can be removed by histone demethylases, and is recognized by reader proteins. H3K36me2 is enriched in intragenic regions and helps establish chromatin domains, regulate gene transcription, and antagonize repressive histone marks such as H3K27me3. The broader biological consequences include facilitating proper gene expression patterns, mRNA processing, and DNA repair (notably in response to double-strand breaks), maintaining genome stability, and influencing development. Disruption of H3K36 methylation is implicated in cancer and developmental disorders, with some oncogenic mutations found in histone H3 lysine 36 or in its modifying enzymes[1][3][5][7]. In summary, H3K36me2 is a critical epigenetic mark that coordinates chromatin structure and gene activity, mainly by serving as a platform for protein recruitment involved in key processes such as transcription and DNA repair. It is not a direct molecular drug target, but enzymes handling its dynamics are emerging as therapeutic targets.

Other names

Histone H3K36me2H3 dimethyl-lysine 36di-methylated H3K36H3K36 dimethylation

Inhibition of H3K36-specific methyltransferases (e.g., NSD2, ASH1L, SMYD2), which reduces H3K36me2 levels and alters chromatin structure and gene expression; Inhibition of demethylases would increase H3K36me2