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

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.