Integrative modeling of Transcription Factor cooperativity and its effects on phenotypic variability

Abstract

The regulation of biological processes relies on a complex nucleotide code embedded in our DNA. Its decoding and interpretation is the main task of Transcription Factors (TFs), which altogether enable the recognition and modulation of gene expression. Whenever factors bind to DNA, a set of additional criteria and conditions need to be satisfied, such as TF concentration, DNA openness, and cooperativity with other binding factors. Such combinations of DNA-bound TFs, as well as their structural and functional cooperativity, allow a more fine-grained control of gene expression due to subtle changes in specificity in both DNA recognition and functional outcomes. This thesis explores the prediction of structural TF cooperativity and its biological consequences. Additionally, examples of functional cooperativity are presented and discussed in the context of neuronal activity and reprogramming. Altogether, this dissertation provides an extensive set of insights to better understand the complex interplay between TFs cooperativity and phenotypes