RT Journal Article
SR Electronic
T1 Disorganization of the histone core promotes organization of heterochromatin into phase-separated droplets
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 473132
DO 10.1101/473132
A1 S. Sanulli
A1 MJ. Trnka
A1 V. Dharmarajan
A1 RW. Tibble
A1 BD. Pascal
A1 A. Burlingame
A1 PR. Griffin
A1 JD. Gross
A1 GJ. Narlikar
YR 2018
UL http://biorxiv.org/content/early/2018/11/18/473132.abstract
AB The heterochromatin protein HP1 is proposed to enable chromatin compaction via liquid droplet formation. Yet, a connection between phase separation and chromatin compaction has not been experimentally demonstrated. More fundamentally, how HP1 action at the level of a single nucleosome drives chromatin compaction remains poorly understood. Here we directly demonstrate that the S. pombe HP1 protein, Swi6, compacts arrays of multiple nucleosomes into phase-separated droplets. Using hydrogen-deuterium exchange, NMR, and mass-spectrometry, we further find that Swi6 substantially increases the accessibility and dynamics of buried histone residues within a mononucleosome. Restraining these dynamics via site-specific disulfide bonds impairs the compaction of nucleosome arrays into phase-separated droplets. Our results indicate that chromatin compaction and phase separation can be highly coupled processes. Further, we find that such coupling is promoted by a counter-intuitive function of Swi6, namely disorganization of the octamer core. Phase separation is canonically mediated by weak and dynamic multivalent interactions. We propose that dynamic exposure of buried histone residues increases opportunities for multivalent interactions between nucleosomes, thereby coupling chromatin compaction to phase separation. We anticipate that this new model for chromatin organization may more generally explain the formation of highly compacted chromatin assemblies beyond heterochromatin.