Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome

Publication Year
2018

Type

Journal Article
Abstract
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.
Journal
Cell
Volume
175
Pages
1481-1491.e13
Date Published
11/2018
ISBN
0092-8674 (Print)0092-8674
Accession Number
30500535

1097-4172Shin, YongdaeChang, Yi-CheLee, Daniel S WBerry, JoelSanders, David WRonceray, PierreWingreen, Ned SHaataja, MikkoBrangwynne, Clifford PHHMI/Howard Hughes Medical Institute/United StatesU01 DA040601/DA/NIDA NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Video-Audio Media2018/12/01Cell. 2018 Nov 29;175(6):1481-1491.e13. doi: 10.1016/j.cell.2018.10.057.