Variability in transcription: promoter architecture, regulatory mutations and noise

SCHOR IE

Colonia

Congreso; 1er CONGRESO BINACIONAL DE LOS CLUBES DEL ARN DE ARGENTINA Y URUGUAY; 2022

CLUBES DEL ARN DE ARGENTINA Y URUGUAY

Gene expression involves a series of tightly regulated steps that allows a certain sequence of the DNA to be expressed into its final product, either protein or RNA. Precise spatio-temporal regulation of this process is crucial to ensure proper development and most functions of a multicellular organism. We therefore expect that gene regulatory networks are robust to intrinsic noise of their components as well as to perturbations, both environmental and genetic. However, it is still not completely understood if robustness can be reached at the level of individual transcriptional regulation events (i.e. control of the expression of specific key genes).We explored how promoters of genes that participate in different physiological and pathological processes are affected by non-coding genetic variability and/or mutations, how this can relate to their promoter architecture and the role of the gene within gene regulatory networks. We also made use of whole-genome sequencing data of breast cancer samples to explore the impact of non-coding mutations in cancer progression and, together with measurements of the activity of breast cancer master regulators, used their recurrence in gene regulatory regions to uncover relevant pathways. Finally, we explored the characteristics of alternative promoters and assessed possible changes in expression noise upon promoter switch.