Light-activated macromolecular phase separation modulates transcription by reconfiguring chromatin interactions

Yoon Jung Kim, Michael Lee, Yi Tsang Lee, Ji Jing, Jacob T. Sanders, Giovanni A. Botten, Lian He, Junhua Lyu, Yuannyu Zhang, Marcel Mettlen, Peter Ly, Yubin Zhou, Jian Xu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Biomolecular condensates participate in the regulation of gene transcription, yet the relationship between nuclear condensation and transcriptional activation remains elusive. Here, we devised a biotinylated CRISPRdCas9–based optogenetic method, light-activated macromolecular phase separation (LAMPS), to enable inducible formation, affinity purification, and multiomic dissection of nuclear condensates at the targeted genomic loci. LAMPS-induced condensation at enhancers and promoters activates endogenous gene transcription by chromatin reconfiguration, causing increased chromatin accessibility and de novo formation of long-range chromosomal loops. Proteomic profiling of light-induced condensates by dCas9-mediated affinity purification uncovers multivalent interaction-dependent remodeling of macromolecular composition, resulting in the selective enrichment of transcriptional coactivators and chromatin structure proteins. Our findings support a model whereby the formation of nuclear condensates at native genomic loci reconfigures chromatin architecture and multiprotein assemblies to modulate gene transcription. Hence, LAMPS facilitates mechanistic interrogation of the relationship between nuclear condensation, genome structure, and gene transcription in living cells.

Original languageEnglish (US)
Article numbereadg1123
JournalScience Advances
Volume9
Issue number13
DOIs
StatePublished - Mar 29 2023

ASJC Scopus subject areas

  • General

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