“HP1 couples disorganization of the histone core to chromatin compaction and droplet formation”
Invited Speaker: Serena Sanulli
Postdoctoral Research fellow in Prof. Geeta Narlikar Lab, Departement of Biochemistry and Biophysics, and Prof. John D. Gross Lab, Department of Pharmaceutical Chemistry, University of California, San Francisco.
Abstract: The heterochromatin protein HP1 is proposed to enable chromatin condensation and liquid droplet formation. Yet, how HP1 action at the nucleosome level drives higher-order chromatin organization remains unclear. Using hydrogen-deuterium exchange, NMR, and crosslinking mass-spectrometry, we show that the S. pombe HP1 protein, Swi6, substantially increases the accessibility and dynamics of buried histone residues within a nucleosome. Restraining these dynamics via site-specific disulfide bonds impairs the ability of Swi6 to bind nucleosomes and to condense chromatin into phase-separated droplets. Our results uncover a counter-intuitive function of Swi6, namely exposing buried regions of the histone octamer to achieve chromatin compaction. We propose that such exposed regions participate in transient multivalent interactions to drive higher-order chromatin organization in heterochromatin. Histone core dynamics may more generally regulate higher-order chromatin assemblies in contexts beyond heterochromatin.