Formation of Chromosomal Domains by Loop Extrusion

• DOI: 10.1016/j.celrep.2016.04.085
• Publication Date: 2016-05-21T05:02:09Z
• Authors: Geoffrey Fudenberg; Maxim Imakaev; Carolyn Lu; Anton Goloborodko; Nezar Abdennur; Leonid A. Mirny
• Keywords: CTCF; Condensin; Interphase

Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms TAD formation remain unclear. Here, we propose that loop extrusion underlies formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, show model produces TADs finer-scale features Hi-C data. Each emerges from multiple dynamically formed through extrusion, contrary typical illustrations single static loops. Loop both explains diverse experimental observations—including preferential orientation CTCF motifs, enrichments architectural proteins boundaries, deletion experiments—and makes specific predictions for depletion versus cohesin. Finally, has potentially far-ranging consequences processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, compaction mitotic chromosomes.