Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness.

Autor: Vanagas L; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina. Electronic address: vanagas@intech.gov.ar., Muñoz D; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina., Cristaldi C; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina., Ganuza A; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina., Nájera R; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina., Bonardi MC; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina., Turowski VR; Laboratorio de Bioquímica y Biología Celular de Parásitos, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA Chascomús, Prov. Buenos Aires, Argentina., Guzman F; Núcleo de Biotecnología Curauma, Pontificia Universidad Católica de Valparaiso, Av. Universidad 330 Curauma, Valparaiso, Chile., Deng B; Department of Biology and VBRN, University of Vermont, VT, USA., Kim K; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Sullivan WJ Jr; Department of Pharmacology and Toxicology, Indiana School of Medicine, Indianapolis, IN 46202, USA., Angel SO; Laboratorio de Parasitología Molecular, INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8.2, C.C 164, B7130IIWA, Chascomús, Prov. Buenos Aires, Argentina. Electronic address: sangel@intech.gov.ar.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Gene regulatory mechanisms [Biochim Biophys Acta Gene Regul Mech] 2023 Sep; Vol. 1866 (3), pp. 194943. Date of Electronic Publication: 2023 May 20.
DOI: 10.1016/j.bbagrm.2023.194943
Abstrakt: Through regulation of DNA packaging, histone proteins are fundamental to a wide array of biological processes. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed histone code that is interpreted by "reader" proteins to modulate chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity. The protozoan parasite Toxoplasma gondii is unique among eukaryotes in possessing a novel variant of H2B designated H2B.Z. The combination of PTMs and the use of histone variants are important for gene regulation in T. gondii, offering new targets for drug development. In this work, T. gondii parasites were generated in which the 5 N-terminal acetylatable lysines in H2B.Z were mutated to either alanine (c-Myc-A) or arginine (c-Myc-R). The c-Myc-A mutant displayed no phenotype over than a mild defect in its ability to kill mice. The c-Myc-R mutant presented an impaired ability to grow and an increase in differentiation to latent bradyzoites. The c-Myc-R mutant was also more sensitive to DNA damage, displayed no virulence in mice, and provided protective immunity against future infection. While nucleosome composition was unaltered, key genes were abnormally expressed during in vitro bradyzoite differentiation. Our results show that regulation of the N-terminal positive charge patch of H2B.Z is important for these processes. We also show that acetylated N-terminal H2B.Z interacts with some unique proteins compared to its unacetylated counterpart; the acetylated peptide pulled down proteins associated with chromosome maintenance/segregation and cell cycle, suggesting a link between H2B.Z acetylation status and mitosis.
Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: