Project

DNA Topoisomerase 1 (Top1) is a major regulator of gene expression with great impact on genome stability. Similarly, Guanine quadruplexes (G4) have recently emerged as critical elements for transcription regulation and potential threats to the genome integrity. Studies of Top1 and G4 have many medical implications since their mutations or deregulations are associated with several pathologies, such as cancers, neurodegenerative diseases or viral infections. A few studies, including ours, have revealed physical and functional interactions between these two elements and their involvement in transcriptional regulation of viral and cellular genes. Our research hypothesis is that this Top1-G4 interaction is involved in a new mechanism of transcriptional regulation. This project aims to test this hypothesis and to determine, genome-wide, the contribution of this interaction on human gene transcriptional regulation. This will be tested using genomic and transcriptomic data obtained on the Top1-dependent transcriptional regulation of cellular genes (RNA-seq data), on the localization of Top1 along the cellular genome (ChIP data) and on the presence of G4 structures at specific foci of this genome (G4Hunter prediction and ChIP data). Results obtained by this bio-informatics analyses, should help us to design new experiments to test our hypothesis, on both retroviral and cellular promoters. In long-term perspectives, this project should reveal new mechanisms of gene transcriptional regulation that could serve for the development of new therapeutic strategies.