Michael Rubinstein, Duke University

Title: The Loops of Life

Abstract: In mammalian cells, the cohesin protein complex is believed to regulate chromatin during interphase through active loop extrusion, in which dynamic loops are formed by cohesin translocating along chromatin. We developed a theoretical model that quantifies how key parameters, including cohesin residence time on chromatin, extrusion velocity, and the number density of chromatin-bound cohesins, regulate genomic contacts. The model describes chromatin contact probabilities and predicts that loop formation probability is a nonmonotonic function of loop length. Our theory demonstrates that active loop extrusion causes the apparent fractal dimension of chromatin to cross over between two and four at contour lengths on the order of 30 kilo-base pairs. This work provides a theoretical basis for the compact organization of interphase chromatin explaining the physical reason for the segregation of topologically associated domains and suppression of chromatin entanglements by up to a factor of 50 which contributes to efficient gene regulation by distal elements such as enhancers or silencers.