Emerging Evidence of Chromosome Folding by Loop Extrusion

• Main Authors: Fudenberg, Geoffrey (Author), Abdennur, Nezar Alexander (Author), Imakaev, Maxim (Author), Goloborodko, Anton (Author), Mirny, Leonid A. (Author)
• Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program (Contributor), Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Massachusetts Institute of Technology. Department of Physics (Contributor)
• Format: Article
• Language: English
• Published: Cold Spring Harbor Laboratory, 2020-05-06T14:42:49Z.
• Subjects: Article
• Online Access: Get fulltext

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. Keywords: genetics; biochemistry; molecular biology.
National Institutes of Health (U.S.) (Grant GM114190)
National Science Foundation. Physics of Living Systems (Grant 15049420)
National Science Foundation. Center for 3D Structure and Physics of the Genome (Grant DK107980)