Post-translational histone modifications and sub-nuclear organization epigenetically influence gene regulation, especially those implicated in antigenic variation of Plasmodium falciparum. Here we screened for histone methylation modifications and determined, for the first time, their spatial nuclear localisation. Differential enrichment in sub-nuclear compartments, suggesting high local concentrations of particular methyl marks was observed. H3-K79me3 particularly, does not co-localise with already defined nuclear compartments, thus apparently defining a compartment not observed previously in other eukaryotes. Our data show the presence of discrete sub-nuclear zones enriched for histone methyl marks, pointing to the existence of specialized transcription factories and repressive regions in Plasmodium.