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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 <jats:italic>Plasmodium falciparum<\/jats:italic> histone acetylome; histone acetyltransferases (<jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s); and histone deacetylases (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s). We describe the genome\u2010wide occurrence of <jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s in the <jats:italic>P. falciparum<\/jats:italic> genome and identify novel, as well as previously unclassified <jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s. We re\u2010confirm the presence of five known <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s and identify, a novel putative <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>. Interestingly, we identify several <jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s with unique and noncanonical domain combinations indicating their involvement in other associated functions. Moreover, the phylogenetic analyses of <jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>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 <jats:styled-content style=\"fixed-case\">HAT<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s of the malaria parasite, investigates their role in drug\u2010resistance generation, and highlights their potential as therapeutic targets.<\/jats:p>","DOI":"10.1111\/febs.14376","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T23:22:43Z","timestamp":1514503363000},"page":"1767-1782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Genome\u2010wide survey and phylogenetic analysis of histone acetyltransferases and histone deacetylases of <i>Plasmodium falciparum<\/i>"],"prefix":"10.1111","volume":"285","author":[{"given":"Abhishek","family":"Kanyal","sequence":"first","affiliation":[{"name":"Department of Biology Indian Institute of Science Education and Research Pashan, Pune 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Biology Indian Institute of Science Education and Research Pashan, Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,12]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"World Malaria Report 2015","author":"World Health 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