INVESTIGADORES
ANGEL Sergio Oscar
congresos y reuniones científicas
Título:
HISTONE VARIANTS AND EPIGENETIC MODULATION OF CHROMATIN IN TOXOPLASMA GONDII
Autor/es:
ANGEL SO*; VANAGAS L
Lugar:
Caxambu
Reunión:
Mesa redonda; XXXIII Annual Meeting of the Brazilian Society of Protozoology / XLIV Annual Meeting on Basic Research in Chagas Disease; 2017
Institución organizadora:
Sociedade Brasileira de Protozoologia
Resumen:
Toxoplasma gondii is a coccidian protozoan parasite that belongs to the phylumApicomplexa. It is estimated that toxoplasmosis exists as a chronicasymptomatic form in 5 hundred million to 1 billion of the world humanpopulation. Although infection with T.gondii is usually asymptomatic in most individuals, it is of great medicalsignificance for pregnant women and immunocompromised patients. In human andother mammals, T. gondii infection ischaracterized by two stages, the rapidly growing tachyzoites, and the latentbradyzoite tissue cysts. These two developmental stages are essential fordisease propagation and causation. Tachyzoite to bradyzoite conversion, andvice-versa, includes a high number of gene expression modifications. It isbelieved that the epigenetic control of gene regulation is crucial for parasitedevelopment, a process that relies on the post-translational modification (PTM)of histones and histone variant exchange. T.gondii possesses the four canonical histones H2A, H2B, H3 and H4 andvariant histones of H3 (H3.3) and H2A (H2A.Z and H2A.X) families.Interestingly, T. gondii has avariant of H2B, that has been named H2B.Z since it dimerizes mainly with H2A.Z.Double variant H2A.Z/H2B.Z nucleosome and H2A.X/H2Ba are not present in thesame genomic regions as it was observed by ChIP-qPCR and ChIP-seq. Moreover,H2A.X is enriched at Telomeric Associates Sequences. These findings reveal thatnuclesomal arrangements are not random in protozoa, highlighting theirrelevance in chromatin composition and regulation. H2A.Z and H2B.Z have shownto be highly acetylated at their N-terminal tails, a marker of activechromatin.  The over-expression of differentH2B.Z mutants, that are unable to acetylate the N-tail, have shown analteration in the differentiation process. On the other hand, proteomicanalysis confirms the presence of gH2A.X in normal conditions suggesting that tachyzoitesmay be subjected to fork collapse and DSB, situations that activate thehomologous recombination repair machinery. H2A.X is phosphorylated at its SQEmotif by ATM kinase at the initial step of HRR pathway. The treatment ofintracellular tachyzoite with KU55933, an ATM inhibitor, produced a significant effect on parasitereplication, suggesting their inhibition effect may be blocking T. gondii DNA replication and/oractivating cell cycle. Taken together the results show that histone variantsand their PTM are important epigenetic regulators in different processes of theparasite life cycle.