Loop extrusion in chromatin: A question of time!*

One important question in the context of the 3D organization of chromosomes is the mechanism of formation of large loops between distant base pairs. Recent experiments suggest that the formation of loops might be mediated by Loop Extrusion Factors like cohesin. Experiments of cohesin have shown that cohesins walk diffusively on the DNA and nucleosomes act as obstacles to the diffusion, lowering the permeability and hence lowering the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low effective diffusion constants leads to times that are unphysically large. The puzzle then is the following, how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple physical answer to this puzzle and show how a naive obstacle view of nucleosomes can be misleading.