An electrostatic repulsion model of centromere organisation.

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Centromeres precisely localize to the chromatin surface during cell division.
• This positioning is crucial for kinetochore-microtubule interactions and genome segregation.
• The physical principles governing centromere surface localization remain largely unknown.

Purpose of the Study:

• To elucidate the physical principles driving centromere surface positioning on mitotic chromosomes.
• To investigate the roles of centromere-associated proteins and chromatin structure in this process.

Main Methods:

• Cellular perturbations
• Biochemical reconstitution assays
• Multiscale molecular dynamics simulations
• Tethering of synthetic charged proteins to chromatin

Main Results:

• Centromere surface localization is driven by repulsion between condensed chromatin and centromere-associated proteins, including CENP-B.
• This localization is independent of condensin-mediated loop extrusion and microtubule engagement.
• Electrostatic repulsion, mediated by negatively charged proteins, is a key determinant of centromere surface positioning.
• Centromere layering emerges from chromatin phase separation, not solely from folding patterns.

Conclusions:

• Electrostatic repulsion dictates centromere surface localization on mitotic chromosomes.
• This mechanism provides a general and programmable strategy for spatial organization of chromatin.
• Findings reveal a novel principle of electrostatic polarity in organizing cellular structures.