Lopez, J. I. P. | Search bioRxiv

bioRxiv2026

Electrostatic control of chromatin compaction safeguards against apoptotic DNA release

Apoptosis involves extensive intracellular reorganisation to facilitate the clearance of dying cells. A key step in this process is the destruction of the genome through fragmentation by caspase-activated endonuclease (CAD). Rather than dispersing after CAD-mediated cleavage, DNA fragments are compacted into a dense chromatin compartment. However, the underlying mechanism and biological relevance of this compaction remain unknown. Here we show that global deacetylation of histone tails promotes chromatin compaction during apoptosis, preventing DNA release into apoptotic extracellular vesicles. Using synthetic effectors that modulate nucleosome electrostatics independently of histone modifications, we demonstrate that electrostatic attraction alone is sufficient to compact and sequester fragmented chromatin. These findings reveal a mechanism by which global reprogramming of histone modifications coordinates fragmentation of the genome with its physical sequestration during apoptosis. Furthermore, our synthetic approach provides a tool to probe the role of physical forces in genome organisation across diverse biological contexts.

cell biology↗

bioRxiv2025

Near-atomistic simulations reveal the molecular principles that control chromatin structure and phase separation

Understanding how chromatins physicochemical properties shape its emergent organisation is central to deciphering genome function. To address this, we present OpenCGChromatin, a high-performance coarse-grained model that achieves near-atomistic simulations of chromatin systems an order of magnitude larger than previously possible, spanning biomolecular condensates and fibers tens of kilobases in length. OpenCGChromatin simulations independently predict, from physicochemical principles, the linker-DNA-dependent chromatin structures observed by cryo-ET and the relative thermodynamic stability of condensates inferred from biochemical assays. Crucially, OpenCGChromatin resolves histone-tail dynamics and interaction networks that remain inaccessible experimentally, explaining how linker-DNA length controls histone tail accessibility and the resulting multiscale structure of chromatin condensates. Extending simulations to 108-nucleosome fibers shows that acetylation disrupts chromatin compaction in a pattern-specific manner by weakening key tail-mediated interactions, with H4K16 and H3K9 emerging as the most energetically disruptive modifications. These results position OpenCGChromatin as a powerful framework for linking molecular detail to emergent chromatin organization.

biophysics↗