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

Authors :
Kim YJ
Lee M Jr
Lee YT
Jing J
Sanders JT
Botten GA
He L
Lyu J
Zhang Y
Mettlen M
Ly P
Zhou Y
Xu J
Source :
Science advances [Sci Adv] 2023 Mar 31; Vol. 9 (13), pp. eadg1123. Date of Electronic Publication: 2023 Mar 31.
Publication Year :
2023

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 CRISPR-dCas9-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.

Details

Language :
English
ISSN :
2375-2548
Volume :
9
Issue :
13
Database :
MEDLINE
Journal :
Science advances
Publication Type :
Academic Journal
Accession number :
37000871
Full Text :
https://doi.org/10.1126/sciadv.adg1123