13/ Proud to share this work led by co-first authors Caelan Bell, Lifeng Chen & Julia Maristany, with contributions from many colleagues across the Rosen, Redding, Collepardo-Guevara & Gerlich labs.

Full story here 👇
🔗 doi.org/10.1101/2025...

12/ In short:
Centromere positioning is not hardwired by folding patterns.
It emerges from physics — specifically, charge-based repulsion.

11/ This modular principle likely extends beyond mitosis — shaping genome organisation in interphase, and offering routes for synthetic control of genome positioning.

10/ Conceptually, it’s like amphiphiles at oil–water interfaces: attraction inside, repulsion outside → stable layering.

9/ Together these findings reveal a general principle:
Centromere layering emerges from electrostatic polarity — a charge-based asymmetry that repels certain domains outward while the rest integrate inward.

8/ We built a synthetic system: TetR fused to a negatively charged GFP.
When tethered to chromatin, this construct drove loci to the surface — in vitro and in cells.

7/ Adding pure DNA segments to nucleosome arrays was enough to push them outward, in cryoET of chromatin condensates and MD simulations.
👉 Negative charge induces surface targeting.

6/ In vitro chromatin condensates and molecular dynamics simulations showed why.
CENP-B’s acidic domain was sufficient to drive nucleosome arrays to the condensate periphery.

5/ When we depleted kinetochores via CENP-C, centromeres shifted inward.
Knocking out CENP-B further reduced surface localisation.
👉 Kinetochores + CENP-B cooperate to position centromeres at the surface.

4/ Even after condensin depletion and spindle depolymerisation, CENP-A centromere cores still localised at the chromosome periphery.
👉 Surface localisation is independent of loops & spindles.

3/ Prevailing models suggested centromeres are placed at the surface by specific chromatin loop architectures. But our work shows this positioning emerges instead from electrostatic repulsion.

2/ Why does this matter?
Centromeres must locate at the chromosome surface to allow kinetochores to attach spindle microtubules. If buried inside, microtubules can’t reach kinetochores to segregate chromosomes faithfully.

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...

Our lab is now on Bluesky! 🚀 Kicking things off by sharing
@fedeteloni.bsky.social latest preprint on the role of cohesin in homology search. Check out the thread for more details!

We also finally landed here!