SET2 is a histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. This protein probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. SET2 binds DNA at promoters, and may act as a transcription activator. SET2 binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. SET2 belongs to a class of huntingtin interacting proteins characterized by WW motifs.