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.

We also finally landed here!