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 DNase (CAD). Rather than dispersing after CAD-mediated cleavage, DNA fragments are compacted into a dense chromatin compartment, but 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 genome fragmentation with its physical sequestration during apoptosis. Our synthetic approach further provides a tool to probe how physical forces contribute to genome organisation across diverse biological contexts.
Authors
- Michael K. Rosen (ORCID: https://orcid.org/0000-0002-0775-7917)
- Maximilian F.D. Spicer (ORCID: https://orcid.org/0000-0001-8286-124X)
- Daniel W. Gerlich (ORCID: https://orcid.org/0000-0003-1637-3365)
- Maria Julia Maristany (ORCID: https://orcid.org/0009-0009-8875-9225)
- Nikki Miguel (ORCID: https://orcid.org/0000-0002-0682-3847)
- Rosana Collepardo‐Guevara (ORCID: https://orcid.org/0000-0003-1781-7351)
- Jose Ignacio Perez Lopez (ORCID: https://orcid.org/0009-0003-7163-8925)
- Lifeng Chen (ORCID: https://orcid.org/0000-0002-9866-8353)
- Jan Huertas (ORCID: https://orcid.org/0000-0003-2607-5214)
- Sanne Wijma
- Mustafa Alaabo
Institutions
- Institute of Molecular Biotechnology (AT)
- University of Vienna (AT)
- Marine Biological Laboratory (US)
- Howard Hughes Medical Institute (US)
- Austrian Academy of Sciences (AT)
- University of Cambridge (GB)
- Max Perutz Labs (AT)
- Vienna Biocenter (AT)
- Medical University of Vienna (AT)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1038/s44318-026-00932-8
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European High Performance Computing Joint Undertaking
- Howard Hughes Medical Institute
- Welch Foundation
- Government of the United Kingdom
- UK Research and Innovation
- Paul G. Allen Frontiers Group
- European Commission
- Boehringer Ingelheim Fonds
- Vienna Science and Technology Fund
- Österreichischen Akademie der Wissenschaften
- Medizinische Universität Wien
- National Institutes of Health
- HORIZON EUROPE Framework Programme
- Engineering and Physical Sciences Research Council
- European Research Council
- H2020 Marie Skłodowska-Curie Actions
- HORIZON EUROPE Marie Sklodowska-Curie Actions