Beautiful new study from @elphegenoralab.bsky.social and Leonid Mirny's lab:
Cohesin-bridged encounters mediate enhancer-promoter communication, predicting how enhancer effect scales with genomic distance and - for the first time - how CTCF sites modulate enhancer-promoter communciation!
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Luca Giorgetti lab @FMI
2/ This is very much in line with and extends our recent discovery that loop extrusion creates rare, but long-lived cohesin-mediated encounters that lasting longer than random contacts and provide support for E-P communication:
šhttps://www.biorxiv.org/content/10.1101/2025.09.24.678119v1.full
5/ Just like in @elphegenoralab.bsky.social and Leonid's study, the hypothesis that long-lived cohesin-driven encounters mediate E-P communication explains how enhancer effect scales with genomic distance (exponentially) and is decoupled from total contact probabilities measured in Hi-C (power-law)
8/ Truly beautiful to see a coherent and predictive physical framework for long-term transcriptional regulation emerge independently from our two teams - Congrats @elphegenoralab.bsky.social @timothyfoldes.bsky.social @karissalhansen.bsky.social and everyone involved. Exciting times for the field!
4/ In our vert recent study we showed that extrusion-driven encounters last susbtantially longer than random contacts:
www.biorxiv.org/content/10.1...
@mattiaubertini.bsky.social @nesslfy.bsky.social
7/ Our studies thus converge on the idea that long-range enhancer-promoter communication depends on long-lived, cohesin-bridged, loop-extrusion-driven encounters mediated by cohesins that land in specific genomic regions depending on whether or not there are CTCF sites, and where they are located:
6/@elphegenoralab.bsky.social & Leonid Mirny's labs' study now brings this concept one level further and shows that the same mechanisms QUANTITATIVELY predicts for the very first time how CTCF site position and orientation determine an enhancer's effect on a distal promoter! This is REALLY exciting.
3/ Cohesin bridges in @elphegenoralab.bsky.social & Leonid Mirny's new study identify with the loop-extrusion-driven long-lived encounters that we recently discovered using polymer simulations and super-high resolution live imaging:
our field may finally be cracking the puzzle of cohesin loop extrusion's role in enhancer! Careful biophysical measurements, engineered loci, and first-principle biophysical thinking are a powerful combo.
An overview of Nora/Mirny lab's preprint+important context by @lucagiorgetti.bsky.social
Luca Giorgetti lab @FMI
Luca Giorgetti lab @FMI
Luca Giorgetti lab @FMI
21/ In very exciting exciting new work using live imaging, @lucagiorgetti.bsky.social measured the duration of cohesin bridges ~ 10s - 2min
This can climb up to ~ 10-30min with CTCF seen by @andersshansen.bsky.social here, @lucagiorgetti.bsky.social here & Christophe Zimmer/Edouard Bertrand here
Luca Giorgetti lab @FMI
Why can't we explain enhancer action despite 2 decades of chromosome conformation technologies? š¬
Our new study spearheaded by Leonid Mirny's group points to a flaw in our assumptions, and to a solution from physical principles
By @timothyfoldes.bsky.social š»& @karissalhansen.bsky.social š§Ŗ
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