Emerging Evidence of Chromosome Folding by Loop Extrusion
- Geoffrey Fudenberg1,5,
- Nezar Abdennur2,3,5,
- Maxim Imakaev3,
- Anton Goloborodko3,4 and
- Leonid A. Mirny3,4
- 1Gladstone Institute of Data Science and Technology, University of California, San Francisco, California 94158
- 2Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
- 3Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
- 4Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
- Correspondence: geoff.fudenberg{at}gmail.com; leonid{at}mit.edu
-
↵5 These authors contributed equally to this work.
Abstract
Chromosome organization poses a remarkable physical problem with many biological consequences: How can molecular interactions between proteins at the nanometer scale organize micron-long chromatinized DNA molecules, insulating or facilitating interactions between specific genomic elements? The mechanism of active loop extrusion holds great promise for explaining interphase and mitotic chromosome folding, yet remains difficult to assay directly. We discuss predictions from our polymer models of loop extrusion with barrier elements and review recent experimental studies that provide strong support for loop extrusion, focusing on perturbations to CTCF and cohesin assayed via Hi-C in interphase. Finally, we discuss a likely molecular mechanism of loop extrusion by structural maintenance of chromosomes complexes.
Footnotes
-
Supplemental material is available for this article at symposium.cshlp.org.
- © 2017 Fudenberg et al.; Published by Cold Spring Harbor Laboratory Press
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted reuse and redistribution provided that the original author and source are credited.
