Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging

被引：249

作者：

Gabriele, Michele ^{[1
,2
,3
]}

Brandao, Hugo B. ^{[1
,2
,3
,13
]}

Grosse-Holz, Simon ^{[4
,5
]}

Jha, Asmita ^{[1
,2
,3
]}

Dailey, Gina M. ^{[6
]}

Cattoglio, Claudia ^{[6
,7
]}

Hsieh, Tsung-Han S. ^{[6
,7
]}

Mirny, Leonid ^{[4
,5
,8
]}

Zechner, Christoph ^{[9
,10
,11
,12
]}

Hansen, Anders S. ^{[1
,2
,3
]}

机构：

[1] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA

[3] Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[4] MIT, Dept Phys, Cambridge, MA 02139 USA

[5] Inst Curie, F-75005 Paris, France

[6] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA

[7] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA

[8] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[9] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany

[10] Ctr Syst Biol Dresden, D-01307 Dresden, Germany

[11] Tech Univ Dresden, Cluster Excellence Phys Life, D-01307 Dresden, Germany

[12] Tech Univ Dresden, Fac Comp Sci, D-01187 Dresden, Germany

[13] Illumina Inc, San Diego, CA 92122 USA

来源：

SCIENCE | 2022年 / 376卷 / 6592期

基金：

美国国家卫生研究院;

关键词：

GENOME; DNA; EXTRUSION; TRACKING; DATABASE; DOMAINS; SITES; WAPL;

D O I：

10.1126/science.abn6583

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the Fbn2 loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. Our results establish that the Fbn2 TAD is highly dynamic, and about 92% of the time, cohesin-extruded loops exist within the TAD without bridging both CTCF boundaries. This suggests that single CTCF boundaries, rather than the fully CTCF-CTCF looped state, may be the primary regulators of functional interactions.

引用

页码：496 / +

页数：70

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