Genome‐wide survey and phylogenetic analysis of histone acetyltransferases and histone deacetylases of Plasmodium falciparum

Malaria parasites can readily sense and adapt to environmental changes, thus making the control and eradication of this disease difficult. Molecular studies have unraveled a very tightly coordinated transcriptional machinery governed by complex regulatory mechanisms including chromatin modification and spatiotemporal compartmentalization. Histone modifying enzymes play key roles in the regulation of chromatin modification and gene expression, which are associated with cell cycle progression, antigenic variation and immune evasion. Here, we present a comprehensive review of the key regulators of the Plasmodium falciparum histone acetylome; histone acetyltransferases ( HAT s); and histone deacetylases ( HDAC s). We describe the genome‐wide occurrence of HAT s and HDAC s in the P. falciparum genome and identify novel, as well as previously unclassified HAT s. We re‐confirm the presence of five known HDAC s and identify, a novel putative HDAC . Interestingly, we identify several HAT s and HDAC s with unique and noncanonical domain combinations indicating their involvement in other associated functions. Moreover, the phylogenetic analyses of HAT s and HDAC s suggest that many of them are close to the prokaryotic systems and thus potential candidates for drug development. Our review deciphers the phylogeny of HAT s and HDAC s of the malaria parasite, investigates their role in drug‐resistance generation, and highlights their potential as therapeutic targets.