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

Science. 2022 Apr 29;376(6592):496-501. doi: 10.1126/science.abn6583. Epub 2022 Apr 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • CCCTC-Binding Factor
  • Cell Cycle Proteins / metabolism
  • Chromatin*
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Cohesins
  • Mice

Substances

  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone