Maintenance of nucleosome organization through replication and transcription counteracts aberrant coalescence of active chromatin.

Authors

R Ciaran MacKenzie Frater, Rikke Rejnholdt Jensen, Joaquim Ollé López, Valentin Flury, Jeroen van den Berg, Jonathan Humbert, Anton Bournonville, Nicolas Alcaraz, Simai Wang, Hannah J Richter, Marty G Yang, Qian Du, Alexander van Oudenaarden, Vijay Ramani, Nils Krietenstein, Anja Groth

Published in

Molecular cell. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

Nucleosomes with their associated modifications organize and regulate the genome. It is unclear how this is integrated with the requirement of replication and transcription to access the DNA template without jeopardizing chromatin function. Here, we reveal a unified requirement for the histone chaperone FACT in mediating nucleosome disruption and reassembly during mammalian replication and transcription. Upon acute FACT depletion, replisome and RNA polymerase progression is halted genome wide, and chromatin structure in their wake collapses, with reduced nucleosome occupancy, irregular spacing, and intermediate assemblies. Chromatin states deteriorate as modified histones are lost due to a lack of histone recycling. Chromatin fiber disorder further manifests in the 3D genome, triggering active genes to coalesce in aberrant microcompartments. Similarly, aberrant compartments form in cells failing to maintain chromatin fiber structure through replication. Nucleosome organization therefore dynamically regulates genome architecture, guarding against spurious chromatin aggregation.

PMID:
42607685
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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