Loop extrusion rules: the next generation

Abstract

The interphase genome of vertebrates contains roughly 100 000 dynamic loops formed by cohesins. These loops are thought to play important roles in many functions, but their exact contribution in each case remains hotly disputed. The key challenge in studying these loops is the lack of a single experimental technique that could reliably and comprehensively visualize their locations and dynamics. Yet, we can infer them using theoretical models that integrate complementary experimental observations. Modeling proved instrumental in showing that cohesins form loops via extrusion. The loop extrusion model made numerous successful qualitative and quantitative predictions and inspired many experiments. However, it also demonstrated limited accuracy in predicting contact maps. Recent research suggests that the original model did not fully account for the intricate details of the mechanism of loop extrusion and its complex regulation. Here, we review the progress in visualizing extrusion and characterizing the cohesin cofactors. These discoveries can be summarized as 'rules' of cohesin movement along chromosomes and incorporated into the next generation of models. Such improved models will enable more accurate inferences of positions and dynamics of cohesin loops and generate better predictions for designing experiments.