Toxoplasma gondii histones H2A: novel features about TgH2A.X

DALMASSO, MC; SULLIVAN JR, WJ; ANGEL, SO

Rosario, Santa Fe, Argentina

Congreso; VIII Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2008

Sociedad Argentina de Protozoología

Toxoplasma gondii is an obligate intracellular parasite. Toxoplasmoses is incurable because of its ability to differentiate from the rapidly replicating tachyzoite stage into a latent cyst form (bradyzoite stage). This stage convertion is regulated at a transcriptional level, but the control of gene expression in apicomplexan parasites is profoundly understudied. Analysis of the Toxoplasma genome database reveals a relatively small number of conventional transcription factors, therefore our hypothesis is that T. gondii employ an unusual gene expression regulatory system that relies heavily on epigenetics. A search in the toxodb.org database was performed and it was possible to identify three H2As: a canonic one (TgH2A.1), and two variants: TgH2A.X and TgH2A.Z. In a previous work we described the presence of a novel H2B variant (TgH2Bv) in T. gondii. Our results showed that TgH2A.Z and TgH2A.1 interacts with TgH2Bv but not TgH2A.X, and the two H2A variants are not present in the same nucleosme. Chromatine immoprecipitation (ChIP) followed by real time PCR showed that they were present in all the regions analized. Eventhough, TgH2A.Z and TgH2Bv were enriched in the active promoter, while TgH2A.X was enriched in the repressed promoters and silenced regions. Finally, the RNA expression of each histone was analyzed in tachyzoite/bradyzoites and in the presence of divers stress and DNA damage agents. Interestingly, TgH2A.X expression was increased in bradizoites. It was also induced in a dose-dependent manner in the presence of H2O2, but it stayed invariable in the treatments with MMS or heat shock.