Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression.

Autor:	Lee J; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA, 16802, USA., Simpson L; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA, 16802, USA.; Department of Chemistry, The Pennsylvania State University, University Park, PA, 16802, USA., Li Y; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA, 16802, USA., Becker S; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA., Zou F; Department of Physics, The Pennsylvania State University, University Park, PA, 16802, USA., Zhang X; Department of Chemistry, The Pennsylvania State University, University Park, PA, 16802, USA., Bai L; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA, 16802, USA.; Department of Physics, The Pennsylvania State University, University Park, PA, 16802, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12.
DOI:	10.1101/2024.02.06.579062
Abstrakt:	Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3D genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast TF Met4 and a few co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form co-localized puncta-like structures in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro . In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes is clustered in 3D in a Met4-dependent manner. A MET3pr -GFP reporter inserted near several native Met4 binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4 binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to methionine depletion. Competing Interests: Conflict of Interest Statement The authors declare no conflict of interest.
Databáze:	MEDLINE
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