Thèse soutenue

Analyse quantitative et fonctionnelle de la dynamique chromosomique : influence du nucléole sur la régulation de l'expression des genes

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Auteur / Autrice : Axel Bernhard Berger
Direction : Olivier GadalHerbert Tschochner
Type : Thèse de doctorat
Discipline(s) : Sciences biologiques
Date : Soutenance en 2008
Etablissement(s) : Paris 11 en cotutelle avec Universität Regensburg, Naturwissenchaftliche Fakultät III
Partenaire(s) de recherche : autre partenaire : Université de Paris-Sud. Faculté des sciences d'Orsay (Essonne)

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Chromatin is distributed non-randomly within the cell nucleus. Its spatial organization has been demonstrated to be important for nuclear metabolism such as, DNA replication, reparation or transcription. I studied the budding yeast HMG-box protein Hmo1. A screen demonstrated that this chromatin-associated protein is genetically linked to the RNA polymerase (Pol) I, to genes coding for ribosomal proteins (RPGs) as well as to genes implicated in stress response. I could show that Hmo1 physically interacts with the rRNA coding gene transcribed by Pol I and with a subset of RPG promoters. Global expression analyses showed a clear dependence on Hmo1 for the expression of a sub-set of RPGs. An hmo1 deletion strain is also largely alleviated in repressing RPG transcription after TOR complex 1 inhibition. These results suggested that Hmo1 is implicated in Pol I transcription as well as RPG regulation. Since Hmo1 is a bona fide nucleolar factor, we wanted to test if Pol II transcribed RPGs associated with Hmo1 are localized in the proximity of the nucleolus. We first developed a new method allowing determination of gene localization probabilities with very high accuracy and with respect to the nucleolus. We could demonstrate by analyzing thousands of cells, that genes are confined into sub-nuclear volumes. These ‘gene territories’ show a locus specific size and can be remodeled upon transcriptional activation. Applying this new method to Pol II transcribed genes required for ribosome biogenesis, such as the RPGs, indicates that the localization of the gene on the chromatin fiber has important implications for its three dimensional positioning.