Bases moléculaires de la sélectivité d'intégration du rétrotransposon Ty1 en amont des gènes transcrits par l'ARN Polymérase III
Auteur / Autrice : | Antoine Bridier |
Direction : | Pascale Lesage |
Type : | Thèse de doctorat |
Discipline(s) : | Biothérapies et Biotechnologie |
Date : | Soutenance en 2014 |
Etablissement(s) : | Paris 7 |
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Mots clés contrôlés
Résumé
Mobile genetic elements are ubiquitous and dynamic components of genomes, and their integration site choice influences genome stability and gene expression. The Tyl retrotransposon of the yeast Saccharomyces cerevisiae is closely related to retroviruses and replicates by reverse transcribing its genomic RNA into cDNA, which is then integrated into the host cell genome. Tyl integrates upstream of RNA polymerase III (Pol III)-transcribed genes, yet, the primary determinant of target specificity has remained elusive. Here, we describe a functional interaction between Tyl integrase and the AC40 subunit of Pol III. Lack of an integrase/AC40 interaction does not significantly affect Tyl integration frequency, however, it dramatically alters target site choice, leading to a major redistribution of Tyl insertion in the genome, principally to regions of heterochromatin. Thus, AC40, through its interaction with Tyl integrase, is the predominant determinant of targeting Tyl integration upstream of genes transcribed by Pol III-transcribed genes.