PT  - JOURNAL ARTICLE
AU  - Geoffrey Fudenberg
AU  - Maxim Imakaev
AU  - Carolyn Lu
AU  - Anton Goloborodko
AU  - Nezar Abdennur
AU  - Leonid A. Mirny
TI  - Formation of Chromosomal Domains by Loop Extrusion
AID  - 10.1101/024620
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 024620
4099  - http://biorxiv.org/content/early/2015/08/14/024620.short
4100  - http://biorxiv.org/content/early/2015/08/14/024620.full
AB  - Characterizing how the three-dimensional organization of eukaryotic interphase chromosomes modulates regulatory interactions is an important contemporary challenge. Here we propose an active process underlying the formation of chromosomal domains observed in Hi-C experiments. In this process, cis-acting factors extrude progressively larger loops, but stall at domain boundaries; this dynamically forms loops of various sizes within but not between domains. We studied this mechanism using a polymer model of the chromatin fiber subject to loop extrusion dynamics. We find that systems of dynamically extruded loops can produce domains as observed in Hi-C experiments. Our results demonstrate the plausibility of the loop extrusion mechanism, and posit potential roles of cohesin complexes as a loop-extruding factor, and CTCF as an impediment to loop extrusion at domain boundaries.