its degree of methylation. Histones can be methylated on lysine (K) and arginine (R) residues only, but methylation is most commonly observed on lysine residues of histone tails H3 and H4. The tail end furthest from the nucleosome core is the N-terminal (residues are numbered starting at this end). Common sites of methylation associated with gene activation include H3K4, H3K48, and H3K79. Common sites for gene inactivation include H3K9 and H3K27. Studies of these sites have found that methylation of histone tails at different residues serve as markers for the recruitment of various proteins or protein complexes that serve to regulate chromatin activation or inactivation. Lysine and arginine residues both contain amino groups, which confer basic and hydrophobic characteristics. Lysine is able to be mono-, di-, or trimethylated with a methyl group replacing each hydrogen of its NH3+ group. With a free NH2 and NH2+ group, arginine is able to be mono- or dimethylated. This dimethylation can occur asymmetrically on the NH2 group or symmetrically with one methylation on each group. Each addition of a methyl group on each residue requires a specific set of protein enzymes with various substrates and cofactors. Generally, methylation of an arginine residue requires a complex including protein arginine methyltransferase (PRMT) while lysine requires a specific histone methyltransferase (HMT), usually containing an evolutionarily conserved SET domain. Different degrees of residue methylation can confer different functions, as exemplified in the methylation of the commonly studied H4K20 residue. Monomethylated H4K20 (H4K20me1) is involved in the compaction of chromatin and therefore transcriptional repression. However, H4K20me2 is vital in the repair of damaged DNA. When dimethylated, the residue provides a platform for the binding of protein 53BP1 involved in the repair of double-stranded DNA breaks by non-homologous end joining. H4K20me3 is observed to be concentrated in heterochromatin and reductions in this trimethylation are observed in cancer progression. Therefore, H4K20me3 serves an additional role in chromatin repression. Repair of DNA double-stranded breaks in chromatin also occurs by homologous recombination and also involves histone methylation (H3K9me3) to facilitate access of the repair enzymes to the sites of damage. Histone methyltransferase The genome is tightly condensed into chromatin, which needs to be loosened for transcription to occur. In order to halt the transcription of a gene the DNA must be wound tighter. This can be done by modifying histones at certain sites by methylation. Histone methyltransferases are enzymes which transfer methyl groups