When K20 is di-methylated on H4, the downstream effect is silencing of genes. This modification is also necessary and sufficient for 53BP1 binding, which is a prerequisite for DNA repair, a highly conserved mechanism. H4K20me2 is associated with hypoacetylation, and inactivation of certain genes. NSD1 and Suv420h1/2 trigger the dimethylation of K20, but only after SET8 catalyzes the mono-methylation of the same lysine, indicating a complex regulation of this modification that can seriously affect replication and stability of genomic information.