Tuesday, August 02, 2022

Structures considered key to gene expression are surprisingly fleeting

Amazing stuff! Possibly a breakthrough! A loopy loop model, which had never before been observed in living cells. Science can be so wrong for so long!

".... A study by MIT scientists suggests that these loops are very dynamic and shorter-lived than previously thought. ...
researchers monitored the movement of one stretch of the genome in a living cell for about two hours. They saw that this stretch was fully looped for only 3% to 6% of the time, with the loop lasting for only about 10 to 30 minutes. The findings suggest that scientists' current understanding of how loops influence gene expression may need to be revised, the researchers say. ..."

"Fleeting chromatin loops
The genome is organized into three-dimensional (3D) domains that are widely thought to be stable, fully looped structures, although this organization has not been directly observed in living cells. Gabriele et al. report the direct visualization of chromatin looping in living cells and use Bayesian inference to quantify looping dynamics. Loops were found to be both rare and short-lived, overturning static models of looping. Instead of being fully looped, 3D genome domains existed overwhelmingly in partially folded configurations. This more dynamic view of 3D genome domains may ultimately allow a deeper understanding of why disruption of some domains and loops causes dysregulation of gene expression in disease."

From the 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."

Structures considered key to gene expression are surprisingly fleeting | Beta site for NSF - National Science Foundation Theories of how loops control gene expression may need to be revised

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging (no public access)

Researchers have discovered that chromatin spends most of its time in a partially looped state


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