Formation of Chromosomal Domains by Loop Extrusion
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Fudenberg-2016-Formation of Chromos.pdf
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Author(s)
Fudenberg, Geoffrey
Imakaev, Maksim Viktorovich
Lu, Carolyn
Goloborodko, Anton
Abdennur, Nezar Alexander
Mirny, Leonid A.
Date Issued
May 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
Fudenberg, Geoffrey, Maxim Imakaev, Carolyn Lu, Anton Goloborodko, Nezar Abdennur, and Leonid A. Mirny. “Formation of Chromosomal Domains by Loop Extrusion.” Cell Reports 15, no. 9 (May 2016): 2038–2049.
Version
Final published version
Abstract
Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. Loop extrusion both explains diverse experimental observations—including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments—and makes specific predictions for the depletion of CTCF versus cohesin. Finally, loop extrusion has potentially far-ranging consequences for processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Physics
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2016.04.085
