Ever wondered how a eukaryotic transcription factor finds its specific DNA motif in the vast genome? In this preprint, we directly measured the dynamics of this search process in living cells, revealing a cooperative mechanism mediated by disordered regions. 1/10 doi.org/10.64898/202...
Huge thanks to everyone involved in this project, @emabiong.bsky.social, @sarapozzi.bsky.social and @alessialoffreda.bsky.social for their dedication, and those that are not on bsky (yet). And to to my science-buddy @samuzambrano.bsky.social: collaborating with you is both a privilege and a joy.
So NF-κB activation amplifies p53 accumulation — yet paradoxically inhibits one of its key protective functions: promoting DNA repair.
Consistent with this prediction, DNA repair became slower under co-stimulation. This effect disappeared in NF-κB knockout cells.
Our model predicted that inflammatory co-stimulation should distort these oscillations into a more sustained p53 response — and live-cell experiments confirmed this shift.
Here comes the fun part. After γ-irradiation, p53 normally oscillates in time. Previous theoretical and experimental work suggests these oscillations promote efficient DNA repair, whereas sustained p53 accumulation is less effective.
This was unexpected — p53 and NF-κB are classically described as antagonists. Looking closer, the TP53 promoter contains conserved NF-κB binding sites. Simulations predicted that higher TP53 synthesis can explain this observation. And indeed: TP53 levels increase upon cytokine co-stimulation.
As expected, treatment with Nutlin-3a (which blocks MDM2-mediated p53 degradation) caused p53 accumulation. But when we added pro-inflammatory cytokines activating NF-κB, p53 accumulated even more. This depends of NF-κB, as p53 is unaffected by cytokines in p65KO cells.
Both p53 and NF-κB show rich nuclear accumulation dynamics. So we engineered MCF-7 cells expressing fluorescently tagged versions of both proteins and followed them in real time using live-cell microscopy during co-stimulation.
What we found surprised us: these two transcription factors cooperate at the molecular level, yet this cooperation produces functional antagonism.
Even more intriguingly, inflammatory signals can impair DNA repair by reshaping the temporal dynamics of p53.
If you’re curious, here’s the story 👇
🧵 I’m very happy to share a new preprint from the @samuzambrano.bsky.social group and ours — a project driven by @emabiong.bsky.social, a PhD student bold enough to tackle a question at the interface of our two expertises: how the biological oscillators p53 and NF-κB talk to each other.
How do dynamics of signalling molecules skew cell fate decisions? With this review we try to move our first steps in the signalling dynamics field, together with the expert lead of @samuzambrano.bsky.social! Kudos to Fulvio, Sara and Erika for their excellent work!
Slightly diminish a band:
They might be quite tall.
Minflux goes to chromatin! Very interesting preprint from @andersshansen.bsky.social lab, featuring co-first author @matteomazzocca.bsky.social, that keeps on making me very proud.
That's so great, Davide! Congratulations!
This looks sooo great! Congratulations @mirlab.bsky.social !!
Great to see you here, Tim!
Happy to share Duyen's and Philipp's work on effective binding energy landscape and affinity of RBPJ obtained in vivo by on- and off-rate measurements is now published. Great collaboration with labs of Franz Oswald and Tilman Borggrefe doi.org/10.1038/s414...
Fantastic Work Christof!
Preprint from Marklund and Greenleaf labs on TF binding: www.biorxiv.org/content/10.1...
In vitro single molecule imaging + In nuclei single molecule footprinting of KLF on engineeered sequences.
On-rates matter more than off-rates, similarly to what previously shown in baceria.
What is the multiscale structure of chromatin condensates? How does it shape thermodynamic and material properties?
We address this at near-atomistic resolution🔥🔥🔥 using cryoET (Rosen & Villa labs, led by H Zhou), a new multiscale model (K Russell) and cryoET-guided sims (J Huertas & J Maristany)
Thank you Laura, you are right! We should have cited that paper!
This looks very interesting! www.science.org/doi/full/10....
On my reading list!
Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters https://www.biorxiv.org/content/10.1101/2025.01.06.631569v1
Towards community-driven visual proteomics! Excited to finally share this large-scale curated & annotated dataset of 1829 high-quality #cryoET tomograms of the little green alga that just keeps giving— Chlamydomonas! 🧪🧶🧬🌾🌊🌍
Preprint📜: www.biorxiv.org/content/10.1...
A short thread🧵👇
Tasty, tasty phase separation. A much needed rigorous study!
Thank you Kazuhiro.Your work was a great inspiration for this! We hope to have reported it accurately.
Thanks Mark, all merit goes to Tom on this! He went through many iterations before having something that was somehow 'accurate' and yet readable.
Excited to share @domenicnarducci.bsky.social 's paper now out in Mol Cell published back-to-back with the paper from @dewitlab.bsky.social - despite lots of prior work, we find that ZNF143 has no looping function
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Thank you Lennart!
