Open AccessDynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Author(s) -
Michele Gabriele,
Hugo B. Brandão,
Simon GrosseHolz,
Asmita Jha,
Gina M. Dailey,
Claudia Cattoglio,
Tsung-Han S. Hsieh,
Leonid A. Mirny,
Christoph Zechner,
Anders S. Hansen
Publication year - 2022
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abn6583
Subject(s) - cohesin , ctcf , chromatin , live cell imaging , microbiology and biotechnology , dynamics (music) , biology , loop (graph theory) , computational biology , dna , cell , genetics , physics , gene , transcription factor , enhancer , mathematics , combinatorics , acoustics
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 theFbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, theFbn2 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 theFbn2 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.
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