Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Author Yongdae Shin, Yi-Che Chang, Daniel Lee, Joel Berry, David Sanders, Pierre Ronceray, Ned Wingreen, Mikko Haataja, Clifford Brangwynne 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. Keywords Animals, Mice, Humans, Female, Male, HEK293 Cells, Cell Line, Tumor, NIH 3T3 Cells, Cytoplasm, Phase Transition, Cell Nucleolus, Chromatin, Genome, Human, Intrinsically Disordered Proteins Journal Cell Volume 175 Issue 6 Pages 1481-1491.e13 Date Published 2018 Nov 29 ISSN Number 1097-4172 DOI 10.1016/j.cell.2018.10.057 Alternate Journal Cell PMCID PMC6724728 PMID 30500535 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML