2016
DOI: 10.1016/j.celrep.2016.04.085
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Formation of Chromosomal Domains by Loop Extrusion

Abstract: Summary Topologically Associating Domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet 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 other f… Show more

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Cited by 1,737 publications
(1,842 citation statements)
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“…Insulation and directionality of the contact footprint of CTCF sites also disappear upon Nipbl deletion (Extended Data Figure 6). However, we observe no effect of Nipbl deletion on CTCF occupancy, demonstrating that the loss of TADs and CTCF contact in ΔNipbl is not due to loss or changes in CTCF occupancy (Extended Data Figure 3), This further strengthens the very distinct roles of CTCF and cohesin in shaping chromosome architecture 14,18 .…”
Section: Disappearance Of Tads and Peakssupporting
confidence: 68%
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“…Insulation and directionality of the contact footprint of CTCF sites also disappear upon Nipbl deletion (Extended Data Figure 6). However, we observe no effect of Nipbl deletion on CTCF occupancy, demonstrating that the loss of TADs and CTCF contact in ΔNipbl is not due to loss or changes in CTCF occupancy (Extended Data Figure 3), This further strengthens the very distinct roles of CTCF and cohesin in shaping chromosome architecture 14,18 .…”
Section: Disappearance Of Tads and Peakssupporting
confidence: 68%
“…Cohesin and CTCF co-localize at TAD boundaries and the bases of Hi-C peaks 7,12 , but their roles are not fully defined. The recently proposed loop extrusion model 14,15 yields predictions that are consistent with experiments. In this model, TADs emerge from the progressive extrusion of chromatin loops by a protein complex (e.g.…”
supporting
confidence: 65%
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