Etude des mécanismes par lesquels les facteurs GATA régulent l'expression des gènes soumis à la répression catabolique azotée chez Saccharomyces cerevisiae

The process of specific gene transcription by RNA polymerase II (Pol II) is initiated by thebinding of specific transcription factors to DNA. A global understanding of the mechanisms of genetranscriptional regulation of Saccharomyces cerevisiae goes through the description of the targets andthe behavior of those transcription factors.The GATA factors are specific transcription factors intervening in the regulation of NitrogenCatabolite Repression (NCR)-sensitive genes, a mechanism encompassing the transcriptionalregulations leading to the preferential use of good nitrogen sources of the growth medium of yeast inthe presence of less good nitrogen sources. Those 4 GATA factors involved in NCR comprise 2activators (Gat1 and Gln3) and 2 repressors (Gzf3 and Dal80).Generally speaking, the promoters of genes have always been described like the main place forthe integration of the transcription regulation signals relayed by the general and specific transcriptionfactors and the chromatin remodeling factors. Furthermore, the GATA factors have been described asintegrating the external signals of nitrogen availability thanks to their specific DNA binding toconsensus GATA sequences in the promoter of NCR-sensitive genes. The results presented hereintroduce many nuances to the model, notably implying new proteins but also new regions in theregulation process of the NCR-sensitive gene regulation. Indeed, the first goal of this work is todiscover and understand the mechanisms of NCR-sensitive gene regulation that will explain thevariations in their expression levels in the presence of various nitrogen sources and their dependencytowards the GATA factors.Strikingly, it appeared that GATA factor positioning was not limited to the promoter, butoccurred also in the transcribed region. It seems that the transcription factors may have been drivenby the general transcription machinery (Pol II). The binding of a chromatin remodeling complex, RSC,has also been demonstrated in the coding region of NCR-sensitive genes. Moreover, the binding of thehistone acetyltransferase complex, SAGA, recruited by the GATA activators, was highlighted alongNCR-sensitive genes. The SAGA complex was also implied in their transcriptional regulation.Finally, a ChIP-sequencing experiment revealed an unsuspected number and diversification oftargets of the GATA factors in yeast, which were not limited to NCR-sensitive genes.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Étude d'une installation ILS de l'aéroport de Bierset

Calcul de l'énergie de déformation par éléments finis à l'aide du logiciel SAMCEFinfo:eu-repo/semantics/publishe

Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes

GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe