Histone H3 and H3.3 variants in the protozoan pathogens Plasmodium falciparum and Toxoplasma gondii.

Histones constitute the fundamental component of chromatin and participate in the regulation of gene expression by virtue of covalent modifications to their N-terminal domains. The discovery that histone-modifying enzymes are targeted by the antiprotozoal agent apicidin has prompted further investigation of gene expression regulation in protozoan parasites; consequently, several chromatin remodeling homologues with unusual features have been isolated. To facilitate investigation of these chromatin remodeling homologues using parasite-specific substrates, we sought to clone and characterize histone H3 from two medically significant pathogens in the phylum Apicomplexa: Plasmodium falciparum (malaria) and Toxoplasma gondii (opportunistic pathogen of immunocompromised individuals). Like most eukaryotic organisms, these parasites each contain at least two histone H3 variants, termed H3 and H3.3. Sequence analysis reveals the Apicomplexan H3 proteins harbor novel and rare features. Expression and purification of recombinant H3 variants will provide species-specific substrate for the analysis of the histone-modifying machinery of these parasites.