Transcription is a moving barrier to loop extrusion that shapes the genome

The protein complex cohesin folds chromosomes by "loop extrusion," through which it extrudes the chromatin fiber into loops. Through interactions with stationary boundary elements, such as CTCF proteins, extrusion generates characteristic patterns of genomic contacts and chromatin spatial organization. Actively translocating elements, such as transcribing RNA polymerase motors, may also act as boundaries, but it has not been established how mobile boundaries might generate spatial genomic patterns. We analyzed chromosome conformation capture (Hi-C) data near active and inactive genes under conditions with normal or altered cohesin dynamics. Based on new observed patterns of genome organization, we developed a "moving barrier" model for transcription-extrusion interactions, in which polymerases impede and push loop-extruding cohesins. We developed a theoretical model to explain how cohesin accumulation results from different cohesin behaviors in the presence of polymerase. The model provides quantitative predictions for the effective boundary strength of active genes, the asymmetry in the boundary, and the dependence of these quantities on gene length. Our analysis demonstrates how the activity of loop-extruding motors can be modulated by other active, mobile elements to spatially organize the genome.