La régulation de la transcription dans les cellules cancéreuses
|Abstract:||Human chromatin, that contain both DNA and numerous binding proteins, is the target of a dynamic and functional multi-scaled compaction, which leads to the regulation of biologic processes as gene expression. In order to define and maintain cellular functions, transcriptional and structural regulatory proteins act together to orchestrate the different genes expression programs. Transcription factors function in a combinatorial and hierarchical manner on regulatory elements within the genome, which are able to generate large topological loops to specifically regulate a target promoter in the right temporal frame. The general co-activator Mediator functions as a center for proper transduction of the transcriptional input, physically connecting regulatory proteins to the transcriptional machinery, to generate a calibrated biological response. Cohesin is implicated into the formation and stabilization of genomic connections at multi-scaled tri-dimensional resolution, which functional features are beginning to be elucidated. Together, transcription factors, Mediator and Cohesin control expression programs that enable the maintenance of cellular identities. Cancerous cells often show deregulations at the transcriptional level, which lead to aberrant expression programs. We demonstrated that regulatory mechanisms, controlling transcription in cancerous cells, obey to the same rules that in normal cells and are conserved, then enable the characterization of key transcription factors that drive cancer progression. We applied this discovery to hormonal resistance in breast cancers. Our results suggest that AP-1 family could be involved into the acquisition of this more aggressive phenotype, by transcriptionally bypassing the drug effects. We proposed that a model for aggressiveness in cancer cells could be through their adaptation to transcriptional treatments, leading to a modulation of key important transcription factors driving transcriptional programs within the cells.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||24 April 2018|
|Collection:||Thèses et mémoires|
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