While SET-2 methylates histone H3K36 during transcription, ASH1 methylates this residue in repressed regions, is important for silencing, and can both positively and negatively influence methylation of histone H3K27.
Post-translational modification of histone H3K36 is not required to suppress cryptic transcription initiation or to include alternative exons in Drosophila; instead it promotes expression of active genes by stimulating polyadenylation.
Mutations in budding yeast modeled after cancer-associated isocitrate dehydrogenase mutations lead to stabilization of heterochromatin and enhanced gene silencing through inhibition of specific histone demethylases by the oncometabolite D-2-hydroxyglutarate.
Mutation of Glycine 34 to Arginine within the N-terminal tail of histone H3 alters post-translational modifications on Lysine 36 and is associated with a delay in replication restart, defective homologous recombination and an increase in genomic instability.
H3-G34R, V, and W oncohistonesin fission yeast cause differential K36 modification, DNA damage sensitivity and genome stability outcomes, highlighting the need for a thorough evaluation of distinct mutations.
Chromatin structure is altered following DNA replication stress through the activity of protein kinase C signalling which leads to functionally coupled histone H3 phosphorylation and acetylation events.