More on link www.biorxiv.org/content/10.1...

This binding influences chromatin conformation, and we hypothesise that high concentrations of Oct4 promote nucleation and further coarsening of clusters on chromatin, aiding in the search for specific binding sites while overall increasing chromatin plasticity through non-specific binding

On a personal note, my favourite part of this project was the research team of amazing scientists behind it, lovely human beings who were a joy to work with!

Very happy and proud of this Rosen/Redding/Collepardo collaborative effort 🔥

also on bky:
@rcollepardo.bsky.social @janhuemar.bsky.social

By merging together experiments (led by Lifeng Chen), with our own coarse-grained simulations, we showcased how experimental and computational approaches can be used in tandem to unveil the molecular mechanisms that drive phase separation.

We also show the ISWI remodeler can slide nucleosomes to “on”✔️ or “off” ❌ spacings, toggling phase separation in vitro and in silico

Arrays with nucleosome spacing closer to a multiple of 10 (the DNA helical periodicity 🧬), are more compact, with increased intra-fiber contacts and lower inter-fiber valency, and form more loose, less stable networks in the condensate

These structural differences dictate condensate behaviour of chromatin arrays.

The key metric? Inter-fiber valency (how many neighbours each fiber contacts).

Higher valency in arrays (namely, arrays close to 10N+5 linkers) make for stronger inter-fiber interactions, and more stable condensates.

We designed nucleosome arrays with different linker DNA lengths, at single base pair resolution, in-vitro and in-silico.

We found that even subtle changes in spacing lead to large-scale structural differences (!)

Nucleosomes—the fundamental units of chromatin—can self-assemble into condensates. But what controls how they assemble?
Spacing between them matters: Just changing the DNA length between nucleosomes, even by a single base pair, dramatically alters how they interact and phase separate.