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.
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging / Gabriele, M.; Brandao, H. B.; Grosse-Holz, S.; Jha, A.; Dailey, G. M.; Cattoglio, C.; Hsieh, T. -H. S.; Mirny, L.; Zechner, C.; Hansen, A. S.. - In: SCIENCE. - ISSN 0036-8075. - 376:6592(2022), pp. 476-501. [10.1126/science.abn6583]
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Zechner C.
;
2022-01-01
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
science.abn6583.pdf
non disponibili
Descrizione: pdf editoriale
Tipologia:
Versione Editoriale (PDF)
Licenza:
Non specificato
Dimensione
1.32 MB
Formato
Adobe PDF
|
1.32 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.