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Tytuł:
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Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density.
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Autorzy:
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Meduri R; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Rubio LS; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Mohajan S; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Gross DS; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA. Electronic address: .
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Źródło:
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The Journal of biological chemistry [J Biol Chem] 2022 Oct; Vol. 298 (10), pp. 102365. Date of Electronic Publication: 2022 Aug 11.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
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MeSH Terms:
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Chromatin*/chemistry
Chromatin*/metabolism
Nucleosomes*/genetics
RNA Polymerase II*/genetics
RNA Polymerase II*/metabolism
Transcription, Genetic*
Glycols*/pharmacology
Chromatin Immunoprecipitation
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Grant Information:
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R01 GM138988 United States GM NIGMS NIH HHS; R15 GM128065 United States GM NIGMS NIH HHS
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Contributed Indexing:
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Keywords: Heat Shock Factor 1; Heat Shock Protein gene coalescence; Msn2/Msn4; RNA Pol II; RNA Pol III; budding yeast; chromatin; hexanediol; phase separation; transcriptional condensates
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Substance Nomenclature:
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0 (Chromatin)
0 (Nucleosomes)
EC 2.7.7.- (RNA Polymerase II)
ZIA319275I (hexamethylene glycol)
0 (Glycols)
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Entry Date(s):
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Date Created: 20220813 Date Completed: 20221110 Latest Revision: 20221130
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Update Code:
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20240104
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PubMed Central ID:
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PMC9486037
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DOI:
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10.1016/j.jbc.2022.102365
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PMID:
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35963432
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Biomolecular condensates are self-organized membraneless bodies involved in many critical cellular activities, including ribosome biogenesis, protein synthesis, and gene transcription. Aliphatic alcohols are commonly used to study biomolecular condensates, but their effects on transcription are unclear. Here, we explore the impact of the aliphatic dialcohol, 1,6-hexanediol (1,6-HD), on Pol II transcription and nucleosome occupancy in budding yeast. As expected, 1,6-HD, a reagent effective in disrupting biomolecular condensates, strongly suppressed the thermal stress-induced transcription of Heat Shock Factor 1-regulated genes that have previously been shown to physically interact and coalesce into intranuclear condensates. Surprisingly, the isomeric dialcohol, 2,5-HD, typically used as a negative control, abrogated Heat Shock Factor 1-target gene transcription under the same conditions. Each reagent also abolished the transcription of genes that do not detectably coalesce, including Msn2/Msn4-regulated heat-inducible genes and constitutively expressed housekeeping genes. Thus, at elevated temperature (39 °C), HDs potently inhibit the transcription of disparate genes and as demonstrated by chromatin immunoprecipitation do so by abolishing occupancy of RNA polymerase in chromatin. Concurrently, histone H3 density increased at least twofold within all gene coding and regulatory regions examined, including quiescent euchromatic loci, silent heterochromatic loci, and Pol III-transcribed loci. Our results offer a caveat for the use of HDs in studying the role of condensates in transcriptional control and provide evidence that exposure to these reagents elicits a widespread increase in nucleosome density and a concomitant loss of both Pol II and Pol III transcription.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
