Seminar

Evolution of gene regulation across 20 mammals

Diego Villar, PhD

Genome sequencing of many mammals has uncovered numerous lineage-specific adaptations in their protein-coding fractions. However, developing a functional understanding of the non-coding regions of mammalian genomes is proving a daunting challenge, in large part because in vivo locations of transcription factor binding evolve rapidly in mammals (reviewed in [Villar et al., Nature Rev. Gen. 2014]). Dr. Diego Villar will present results derived from a detailed characterisation of the evolution of promoter and enhancer activity across twenty mammalian species that combines whole-genome ChIP-seq experiments and computational approaches [Villar et al., Cell, 2015]. These findings may revise earlier models of transcriptional regulation, and raise important questions on (i) the contribution of individual enhancers to gene expression and (ii) the evolution of tissue-specific regulatory regions. (i) Villar D, Flicek P, Odom DT. "Evolution of transcription factor binding in metazoans - mechanisms and functional implications" Nature Reviews Genetics (2014) 15(4):221-33 (ii)Villar D*, Berthelot C*, Aldridge S, Rayner TF, Lukk M, Pignatelli M, Park TJ, Deaville R, Erichsen JT, Jasinska AJ, Turner JM, Bertelsen MF, Murchison EP, Flicek P, Odom DT. "Enhancer evolution across 20 mammalian species" Cell (2015) 160(3):554-66 Moreover, the identification of many enhancers whose activity is only detected in a single species (out of twenty analysed) could provide opportunities for the identification of lineage-specific regulatory adaptations driving biomedically-relevant phenotypes, such as hypoxia tolerance or cancer resistance - research questions that Diego aims to tackle.