Monomethylation of lysine-21 of histone H4 (H4K20) is performed by SETD8 (KMT5A) (Yin et al. 2005). Trimethylation, performed by SUV420H1 and SUV420H2 and possibly SMYD3 (Foreman et al. 2011), is associated with heterochromatin formation and gene repression (Schotta et al. 2004).