Histones are highly conserved proteins that serve as the structural scaffold for the organization of nuclear DNA into chromatin. The four core histones, H2A, H2B, H3, and H4, assemble into an octamer (2 molecules of each). Histones are modified post-translationally by the actions of enzymes in both the nucleus and cytoplasm. These modifications, which include acetylation, phosphorylation, methylation, and ubiquitin-ation, occur predominantly on the N-terminal and C-terminal tails that extend beyond the nucleosome core particle. Trimethylation of histone H4 on lys20 (H4-K20me3) selectively marks constitutive pericentromeric hetero-chromatin and imprinting control regions, while mono- and dimethylation are broadly distributed but principally enriched in euchromatin regions. Although the biological function of H4K20me remains poorly understood, studies suggest that H4-K20me2 is involved in the guidance of DNA repair proteins to DNA strand breaks, whereas H4K20me1 is associated with chrom