SET8-Mediated Methylations of Histone H4 Lysine 20 Mark Silent Heterochromatic Domains in Apicomplexan Genomes

Enzymes of the SET family, namely histone lysine methyltransferases (HKMT) mediate the promotion or repression of genes, depending on their methylation activity at certain lysine residues on H3. Sautel et al shows that the SET8 enzyme of medically important parasites, Plasmodium sp and Toxoplasma gondii, members of the Apicomplexan genus, methylates lysine residue 20 on H4 (H4K20) in vivo.

Historically, it is thought that methylation of H4K20 played a pivotal role in DNA integrity and repair. Recently, methylation activity at H4K20 has been linked to gene silencing and cell cycle signalling. Moreover, this study finds that parasitic SET8 has mono-, di-, and trimethylase activity, unlike the SET8 enzymes of higher eukaryotes which display only monomethylase activity.

This study provides some insight into the substrates required and biochemical pathways used by metozoan parasites during growth, differentiation and parasitic life cycle. Although a vaccine or anti-protozaon targeted at an enzyme possessed by both host and parasite could lead to cytotoxicity in the host, further characterization of the enzymes involved in the complicated life cycle of the parasites may lead to the development of an effective agent to break the parasitic life cycle.

Katrina McMahon 40094797