“Doctor of Philosophy” by Naomi Habib

Transcription regulation plays a central role in the activity of living cells and in their response to internal or external stimuli. This complex regulatory process is mediated by multiple interacting mechanisms. These mechanisms include both sequence specific binding proteins called transcription factors, and epigenetic mechanisms, including DNA methylations and chromatin modifications, as well as non-coding regulatory RNAs. Changes in gene regulation have been postulated to play a key role in generating the wide phenotypic diversity observed across species. Yet the evolutionary driving forces and the dynamics of this evolutionary process are largely unknown. I studied this process from two different perspectives. Cis-regulatory evolution Regulation of gene expression can evolve through mutations in the DNA sequence leading to altered activity of trans acting factors such as transcription factors, or to changes in cis-regulatory sequences at promoter and enhancer regions, which affect the binding of regulatory proteins. While trans acting factors are largely conserved, large-scale changes in cis-elements were observed for specific factors in organisms as diverse as yeasts, flies, an