Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Amy Strom, PhD Candidate
Department of Molecular and Cell Biology
UC Berkeley and Department of Biological Sciences and Engineering
Lawrence Berkeley National Laboratory

Compartmentalization is a theme used throughout all kingdoms of biology to create functionally distinct units within a complex cellular environment. In addition to membrane-bound organelles, compartments can exist in the cell that are not membrane bound, yet are still physically distinct from surrounding space. The cell contains a number of these membraneless organelles (nucleoli, stress granules, PML bodies, etc.), which are thought to be formed by liquid-liquid phase separation. Constitutive heterochromatin is a nuclear domain containing highly repetitive, gene-poor DNA sequences that must be transcriptionally silenced in order to maintain genome integrity. The canonical model of heterochromatic silencing invokes high compaction of histones in order to sterically prevent large proteins like polymerases from accessing heterochromatic sequences. However, we find that heterochromatin in both insect and mammalian cells has properties of a phase-separated domain, providing an alternate hypothesis for protein exclusion; based on selective permeability rather than steric hindrance. We find that, similar to other membraneless organelles, the heterochromatin domain is indeed capable of liquid-like fusion, is selectively permeable, and the hetero-euchromatic interface is a barrier to protein diffusion. Additionally, Drosophila HP1a protein is capable of liquid demixing in vitro and mediates domain formation in vivo. It has been suggested that phase separation could be a general organizing property for many cellular bodies; therefore this model has broad implications for understanding the mechanism of nuclear organization.