title: Toxoplasma histone acetylation remodelers as novel drug targets.
abstract: Toxoplasma gondii is a leading cause of neurological birth defects and a serious opportunistic pathogen. The authors and others have found that Toxoplasma uses a unique nucleosome composition supporting a fine gene regulation together with other factors. Post-translational modifications in histones facilitate the establishment of a global chromatin environment and orchestrate DNA-related biological processes. Histone acetylation is one of the most prominent post-translational modifications inﬂuencing gene expression. Histone acetyltransferases and histone deacetylases have been intensively studied as potential drug targets. In particular, histone deacetylase inhibitors have activity against apicomplexan parasites, underscoring their potential as a new class of antiparasitic compounds. In this review, we summarize what is known about Toxoplasma histone acetyltransferases and histone deacetylases, and discuss the inhibitors studied to date. Finally, the authors discuss the distinct possibility that the unique nucleosome composition of Toxoplasma, which harbors a nonconserved H2Bv variant histone, might be targeted in novel therapeutics directed against this parasite.
authors.affiliation: Laboratorio de Parasitología Molecular, IIB-INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, (B7130IIWA), Chascomús, Prov. Buenos Aires, Argentina. vanagas@intech.gov.ar
authors.forename: Laura
authors.initials: L
authors.lastname: Vanagas
authors.forename: Victoria
authors.initials: V
authors.lastname: Jeffers
authors.forename: Silvina S
authors.initials: SS
authors.lastname: Bogado
authors.forename: Maria C
authors.initials: MC
authors.lastname: Dalmasso
authors.forename: William J
authors.initials: WJ
authors.lastname: Sullivan
authors.forename: Sergio O
authors.initials: SO
authors.lastname: Angel
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000977:Antiparasitic Agents / Q000627:therapeutic use; D002843:Chromatin / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D014122:Toxoplasma / Q000235:genetics*; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000977:Antiparasitic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases