Jan Huertas

New paper alert from the group!! 🚨: DNA flexibility tips the balance between stability and plasticity in nucleosomes

One of the works from my PhD, co-led alongside @nachper.bsky.social, is finally out! Work from @rcollepardo.bsky.social & @janhuemar.bsky.social
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www.biorxiv.org/content/10.6...
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How do DNA sequence and histone chemistry tune nucleosome stability and plasticity?

Check out our latest work to find out. Now available on bioRxiv!

www.biorxiv.org/content/10.6...

@juliamaristany.bsky.social
@janhuemar.bsky.social
@rcollepardo.bsky.social

Share with your colleagues!!

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A Goldilocks zone of DNA flexibility defines stable yet plastic nucleosomes, tuned by histone chemistry https://www.biorxiv.org/content/10.64898/2026.02.16.706184v1

New preprint alert! Very proud of this work, lots of hard work that turned into a really cool story!

This was my first chance to step into a senior role, but most importantly, it means far more to me than just the science.
You should always say yes to new projects.

www.biorxiv.org/content/10.6...

Visualising the creation of biomolecular condensates A Junior Research Fellow at St Catharine's is part of an international team of scientists responsible for a long-awaited visualisation of liquid droplets forming inside a cell nucleus known as condensates, which help regulate essential processes such as gene expression, DNA repair and stress responses.

Congratulations to @janhuemar.bsky.social (JRF at Catz since 2023) who is part of an international team of scientists responsible for a long-awaited visualisation of liquid droplets forming inside a cell known as condensates, key for processes such as DNA repair: caths.cam.ac.uk/cond... @cam.ac.uk

Congratulations Alberto!
Looking forward to read it!

Super excited to share that our paper is now out in @science.org. Lots of work, but also lots of fun getting this out.
Be sure to check it out!
www.science.org/doi/10.1126/...
Also, follow:
@huabin-zhou.bsky.social @juliamaristany.bsky.social @kieran-russell.bsky.social @rcollepardo.bsky.social

Very excited to present OpenCGChromatin🔥🔥🔥

A new coarse-grained model that probes full chromatin condensates at near-atomistic resolution to reveal the molecular regulation of chromatin structure and phase separation

Brilliantly led by @kieran-russell.bsky.social, with the Rosen and Orozco groups

So exciting to see this amazing paper out! Many thanks to @jojdavies.bsky.social for inviting us to contribute with our models to this fascinating story!

@rcollepardo.bsky.social @juliamaristany.bsky.social

Oct4 clusters promote DNA accessibility by enhancing chromatin plasticity Pioneer transcription factors are defined by their ability to engage closed chromatin and render it accessible. Oct4, a master regulator of pluripotency, exemplifies this capacity as it can bind nucle...

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...

A mechanism for Oct4 binding to closed chromatin. We hypothesize that the sampling of inaccessible regions of the genome might be aided by the formation of clusters that grow bigger in the presence of chromatin, facilitating the finding of specific target genes in cellular reprogramming.

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 size of the Oct4 clusters is significantly bigger in the presence of chromatin

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.

Oct4 prefers to bind Linker DNA, even if binding to nucleosomal DNA is still significant. The NRL has a non-trivial effect in the modes of binding

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...

Binding of Oct4 to different Nucleosomal Repeat Lengths (167, 172, 177, 182)

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.

A rendering of multiple Oct4 molecules bound to a chromatin fibre

🚨 🚨 🚨 New preprint alert!!! 🚨 🚨 🚨
In the past, we have learnt that Oct4 can induce nucleosome breathing on the mono-nucleosome level.
But what happens when you have a fibre of multiple nucleosomes?
www.biorxiv.org/content/10.1...
@rcollepardo.bsky.social @juliamaristany.bsky.social

An electrostatic repulsion model of centromere organisation During cell division, chromosomes reorganise into compact bodies in which centromeres localise precisely at the chromatin surface to enable kinetochore-microtubule interactions essential for genome se...

1/ New preprint alert!
In collaboration between the Rosen, Redding, Collepardo-Guevara & Gerlich labs, we uncover a surprising principle of chromosome organisation: electrostatic repulsion positions centromeres at the chromosome surface during mitosis.
🔗 doi.org/10.1101/2025...

Nucleosome spacing can fine-tune higher-order chromatin assembly - Nature Communications Internucleosomal linker length alters the stability and dynamics of chromatin condensates by shifting the balance between inter- and intramolecular interactions. Further, by changing the linker length...

🚨 New paper out in Nature Comms!

From the Rosen, Redding and Collepardo Labs, we uncover how #nucleosome spacing fine-tunes the architecture of #chromatin condensates.

👇 A short thread on how physical #genome organization emerges from molecular interactions:

www.nature.com/articles/s41...

So excited to finally see our CTPR-condensate work published! Well done Chris, Mateo, Julia et al. ❤️ @chemicalscience.rsc.org @phar.cam.ac.uk @rcollepardo.bsky.social @juliamaristany.bsky.social
doi.org/10.1039/D5SC...

🌱Join us for the first #FragileNucleosome seminar of this spring! We are excited to host @juliamaristany.bsky.social & @chribue.bsky.social this week!
If you have registered before you can join from the same link, if not, don't forget to register!
us06web.zoom.us/webinar/regi...

Excited to share our newest collaboration with @kazu-maeshima.bsky.social and @masaashimazoe.bsky.social, where we show that H1 acts as a liquid-like glue in chromatin.
Go check the paper on the biorXiv!

Cold-induced nucleosome dynamics linked to silencing of Arabidopsis FLC Temperature influences nucleosome dynamics, and thus chromatin, to regulate gene expression. Such mechanisms underlie the epigenetic silencing of Arabidopsis FLOWERING LOCUS C (FLC) by prolonged cold....

We are happy to share our work on local #nucleosome dynamics integrating #temperature inputs into an #epigenetic switching mechanism.

⚠️ Preprint alert!!
www.biorxiv.org/content/10.1...

Disrupting droplets Mutations in certain protein regions have predictable effects on the stability of cellular droplets and the risk of harmful protein clumps forming inside them.

Proud to have the final version of our paper on mutations + condensates + scaling laws published in @elife.bsky.social! Work led by @juliamaristany.bsky.social w/ @rcollepardo.bsky.social ! Read the digest here: elifesciences.org/digests/9906...

Are you in #BPS2025?

Come to join us at the MGO Symposium this afternoon!

Who's going to #BPS2025?

Please join us at the MGO Symposium @mgo-bps.bsky.social on Saturday 1:30 pm Room 511ABC

Featuring experiments, simulations, and all the scales by
@serenasanulli.bsky.social @melikel.bsky.social
@maristizabal.bsky.social @janhuemar.bsky.social and more

Please repost! 🚀✨

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

[2/6] How’d we do it? High-resolution cryo-ET captured chromatin condensates at nanometer detail, while simulations brought the histone tails and nucleosome dynamics to life. Together, these tools showed how molecular interactions drive mesoscale chromatin behavior.