Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome.

TitleLiquid Nuclear Condensates Mechanically Sense and Restructure the Genome.
Publication TypeJournal Article
Year of Publication2018
AuthorsShin, Y, Chang, Y-C, Lee, DSW, Berry, J, Sanders, DW, Ronceray, P, Wingreen, NS, Haataja, M, Brangwynne, CP
JournalCell
Volume175
Issue6
Pagination1481-1491.e13
Date Published2018 11 29
ISSN1097-4172
KeywordsAnimals, Cell Line, Tumor, Cell Nucleolus, Chromatin, Cytoplasm, Female, Genome, Human, HEK293 Cells, Humans, Intrinsically Disordered Proteins, Male, Mice, NIH 3T3 Cells, Phase Transition
Abstract

<p>Phase transitions involving biomolecular liquids are a fundamental mechanism underlying intracellular organization. In the cell nucleus, liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is implicated in assembly of the nucleolus, as well as transcriptional clusters, and other nuclear bodies. However, it remains unclear whether and how physical forces associated with nucleation, growth, and wetting of liquid condensates can directly restructure chromatin. Here, we use CasDrop, a novel CRISPR-Cas9-based optogenetic technology, to show that various IDPs phase separate into liquid condensates that mechanically exclude chromatin as they grow and preferentially form in low-density, largely euchromatic regions. A minimal physical model explains how this stiffness sensitivity arises from lower mechanical energy associated with deforming softer genomic regions. Targeted genomic loci can nonetheless be mechanically pulled together through surface tension-driven coalescence. Nuclear condensates may thus function as mechano-active chromatin filters, physically pulling in targeted genomic loci while pushing out non-targeted regions of the neighboring genome. VIDEO ABSTRACT.</p>

DOI10.1016/j.cell.2018.10.057
Alternate JournalCell
PubMed ID30500535
PubMed Central IDPMC6724728
Grant List / HHMI / Howard Hughes Medical Institute / United States
U01 DA040601 / DA / NIDA NIH HHS / United States