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Etude des mécanismes épigénétiques impliqués dans la kystogénèse chez le pathogène humain Toxoplasma gondii

Abstract : The intracellular parasite Toxoplasma gondii is the pathogen responsible for toxoplasmosis. This opportunistic parasite causes cerebral toxoplasmosis in immunodepressed individuals and the fetus. Interconversion from the virulent tachyzoïte form of the parasite to its quiescent bradyzoïte form is a critical point in the pathogenesis. This process involves a coordinated regulation of the expression of genes in the parasite, which results in a cascade of molecular events at the level of DNA. Studies suggest a transcriptional control of interconversion, including a stage specific expression of genes. However, this parasite and the whole phylum Apicomplexa are characterised by a quasi-shortage of specific transcription factors. We hypothesised that the level of expression of genes in toxoplasma is narrowly regulated by physical structure and chemical nature of chromatin. This manuscript illustrates the major influence of the “histone code” on parasite differentiation. We identified enzymes which are responsible for editing this code. The most striking example is the discovery of a methyltransferase TgCARM1 which methylates the arginine-17 residue of the histone H3, which is a marker of transcription activation. We also identified the first co-repressor complex of Toxoplasma (TgCRC). TgCRC partly controls the acetylation/deacetylation balance, in opposition to the acetylase TgGCN5, which influences parasitic differentiation. Our results leads mainly to the idea of the existence of a highly sophisticated "parasitic histone code", which has co-evoluated with that of the parasitized host cell.
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https://tel.archives-ouvertes.fr/tel-00011144
Contributor : Nehmé Saksouk <>
Submitted on : Tuesday, December 20, 2005 - 4:53:27 PM
Last modification on : Friday, November 6, 2020 - 3:48:56 AM
Long-term archiving on: : Friday, September 14, 2012 - 4:11:17 PM

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  • HAL Id : tel-00011144, version 1

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Nehmé Saksouk. Etude des mécanismes épigénétiques impliqués dans la kystogénèse chez le pathogène humain Toxoplasma gondii. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00011144⟩

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