Congratulations Alberto!
Looking forward to read it!

I couldn't have done this without the support of @rcollepardo.bsky.social and @juliamaristany.bsky.social. It's been really fun working with them, and I managed to get them hyped about my favourite protein.
Hoping this paper will also get you excited about Oct4!
www.biorxiv.org/content/10.1...

We propose that the reshaping of chromatin and the binding in a cluster-like manner can be one of the solutions to the so-called search problem. We hypothesize that this binding in high concentrations of Oct4 might be key to explaining how silenced genes are activated in cellular reprogramming.

The formation of these clusters is agnostic to the presence of nucleosomes. But they grow significantly larger when they are bound to chromatin! Chromatin acts as a flexible scaffold that concentrates Oct4 molecules and promotes their coalescence into larger clusters.

The binding to chromatin is happening preferentially to the free DNA regions, almost exclusively via the DNA-binding domains. This leaves the long, disordered activation domains free to interact with each other and promote the formation of Oct4 clusters...

Using our near-atomistic coarse grained model, we have simulated the effect of having varying Oct4 concentrations in a 12-nucleosome chromatin fibre. We show that the binding of Oct4 rearranges chromatin, making it more irregular, in a way that depends on the chromatin linker length.

Thanks a lot Srinjan!

[6/6] Our work bridges molecular structure, mesoscale organization, and phase separation in chromatin condensates. I only highlighted the simulations results, but there is a lot more! Go read the preprint for the full story: www.biorxiv.org/content/10.1...

[5/6] Here we saw that 25 bp chromatin builds inter-fiber networks with abundant, strong intermolecular interactions leading to stable condensates, whereas in the 30bp, the tails are mainly forming intra-fiber contacts, making intermolecular contacts weaker.

[4/6] Moreover, using a combination of the experimental data and our minimal model, we were able to get a high resolution reconstruction of an interaction cluster with all the nucleosome tails!

[3/6] Our simulations allowed us to explore the different chromatin structures:
The 25 bp chromatin forms flexible, heterogeneous structures with diverse tail interactions, whereas the 30 bp chromatin favors compact, rigid (and very ordered) stacking with lots of inter-nucleosome contacts