טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentIsakov Elada
SubjectTrichostatin A Regulates Peroxiredoxin Expression and
Virulence of the Parasite Entamoeba
histolytica
DepartmentDepartment of Medicine
Supervisor Professor Serge Ankri
Full Thesis textFull thesis text - English Version


Abstract

The acetylation of the core histone N-terminal "tail" domains is recognized as a highly conserved mechanism for regulating chromatin functional states. This reversible mechanism is regulated by the opposing activities of histone acetyltransferases and histone deacetylases. The role of histone modifications in the regulation of Entamoeba histolytica genes expression is largely unknown. Histone acetylase and deacetylase activities have been previously described in this protozoan parasite. This information directed us to the hypothesis that the mechanism of regulation of gene expression through histone acetylation may exit in the parasite E.histolytica. First we examined the effect of Trichostatin A, a histone deacetylase inhibitor, on the acetylation status of the parasite's histones. We saw that TSA caused upregulation of H4 acetylation. Next, we examined the effect of TSA on E.histolytica virulence. We showed that TSA treated trophozoites had higher cytopathic and hemolytic activities and a better resistance to oxidative stress compared to untreated trophozoites. We first focused our attention on peroxiredoxin, a protein previously associated with E.histolytica resistance to oxidative stress and virulence. We found that the expression of peroxiredoxin is reversibly upregulated by TSA. A genomic approach shows that additional key genes participating in virulence, such as the galactose-inhibitable lectin small subunits have their expression upregulated by TSA. Our work confirm the hypothesis that histone acetylation play a critical role in the regulation of virulence genes in the parasite E.histolytica.