Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
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- Michele Gabriele
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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- Hugo B. Brandão
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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- Simon Grosse-Holz
- Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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- Asmita Jha
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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- Gina M. Dailey
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
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- Claudia Cattoglio
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
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- Tsung-Han S. Hsieh
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
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- Leonid Mirny
- Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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- Christoph Zechner
- Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
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- Anders S. Hansen
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
説明
<jats:p> 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 <jats:italic>Fbn2</jats:italic> TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the <jats:italic>Fbn2</jats:italic> 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 <jats:italic>Fbn2</jats:italic> 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. </jats:p>
収録刊行物
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- Science
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Science 376 (6592), 496-501, 2022-04-29
American Association for the Advancement of Science (AAAS)
