Space odyssey: characterizing transcriptional regulation at a distance

In this thesis, we delved into the rules governing how our genetic material is organized from three distinct angles. First, we developed a novel system that enables us to explore the intricate interplay between gene expression and cohesin-dependent loop extrusion within a single stretch of DNA inside a cell. We observed that when local loop extrusion becomes more active, it can counteract active gene expression. Next, we uncovered a new class of enhancers that we termed “topological enhancers”. These enhancers primarily function to recruit cohesin complex, which in turn shape the local folding of DNA and, consequently, activate gene expression. Lastly, we identified de novo silencers that can turn off expression of genes located far away in the genome.