– Histone-lysine N-methyltransferase SUV42H2, also known as Suppressor of variegation 4-2 homolog 2, Su(var)4-2 homolog 2, Lysine N-methyltransferase 5C, SUV42H2 and KMT5C, is nucleus protein that belongs to the histone-lysine methyltransferase family and Suvar4-2 subfamily. SUV42H2 is a histone methyltransferase that specifically trimethylates ‘Lys-2’ of histone H4. H4 ‘Lys-2’ trimethylation represents a specific tag for epigenetic transcriptional repression. SUV42H2 mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. SUV42H1 is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2). FRAP experiments reveal that SUV42H2 is strongly associated with pericentric heterochromatin. The fraction of SUV42H2 captured and characterized by TAP/MS is a soluble fraction which may be in a stable association with HP1. SUV42H2 may be recruited to heterochromatin in association with HP1, and stably maintained at its heterochromatin sites in an HP1-independent fashion.