INVESTIGADORES
ANGEL Sergio Oscar
congresos y reuniones científicas
Título:
Study of the biological importance of Toxoplasma gondii H2B.Z histone and function of its acetylated lysines
Autor/es:
MUNOZ D; GANUZA A; NARDELLI SC; SULLIVAN WJ; KIM K; ANGEL SO; VANAGAS L
Lugar:
Quinidio
Reunión:
Congreso; International Toxoplasma Congress XV; 2019
Institución organizadora:
Toxoplasma meeting
Resumen:
T. gondii,as well as other apicomplexas, presents a unique H2B variant, H2B.Z, whichshares nucleosome and features with H2A.Z (genome localization and N-tailacetylation), composing a unique double variant nucleosome. The existence of aunique H2B variant in T. gondii offers an interesting matter of study tofind new biological pathways and putative drug targets. H2A.Z and H2B.Z arepositioned at transcription start sites (TSS) together with H3K4Me3 and bothhistone variants showed to be highly acetylated at N/terminal tail. Todetermine the biological importance of this histone and its N-terminal 5acetylatable lysines, it was generated some constructions changing theacetylable lysines by the neutral aminoacid alanine (c-Myc-A) or by thepositively charged arginine (c-Myc-R), each tagged with c-Myc, to generate T. gondii Pru lines overexpressing thismutant and the wilde type version as control together the endogenous H2B.Z(c-Myc-wt/H2B.Z, c-Myc-A/H2B.Z and c-Myc-R/H2B.Z). Parasites did not showsignificative differences in the replication rates, but we observed anincrement in the differentiation rate for c-Myc-R/H2B.Z line compared withparental, while c-Myc-A/H2B.Z had a lower differentiation rate (1.88 and 0.74relative to parental taken as 1, respectively). c-Myc-wt/H2B.Z ? ?valores?   Since H2B.Z gene is an essential gene, here wegenerated new mutant lines by disruption of the endogenous H2B.Z gene by usingCRISPR/Cas9 in the lines over-expressing the mutant histones to generate c-Myc-A/KOand c-Myc-R/KO T. gondii lines.Phenotypic analysis has shown similar results to those obtained with theover-expressing lines: there is an increment in the differentiation rate inc-Myc-R/KO parasites, and a lower differentiation rate in c-Myc-A/KO also whenthe endogenous histone was deleted. In conclusion, acetylations in theN-terminal region of H2B.Z histone would be important for the differentiationof the parasite.