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Maintenance of nucleosome organization through replication and transcription counteracts aberrant coalescence of active chromatin [TTchem-seq]


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 of the histone chaperone FACT in mediating nucleosome disruption and re-assembly in 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE287763 | GEO | 2026/08/17

REPOSITORIES: GEO

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