Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response.
3D genome
Hsf1
Mediator
RNA Pol II
biomolecular condensates
chaperone
gene transcription
heat shock response
inter-chromosomal interactions
phase separation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
17 11 2022
17 11 2022
Historique:
received:
15
10
2021
revised:
28
08
2022
accepted:
10
10
2022
pubmed:
4
11
2022
medline:
23
11
2022
entrez:
3
11
2022
Statut:
ppublish
Résumé
Mammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, whereas an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become constitutively active without intergenic coalescence, which comes at a fitness cost. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control.
Identifiants
pubmed: 36327976
pii: S1097-2765(22)00970-4
doi: 10.1016/j.molcel.2022.10.013
pmc: PMC9701134
mid: NIHMS1848036
pii:
doi:
Substances chimiques
HSP70 Heat-Shock Proteins
0
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4386-4399.e7Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM138689
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM138988
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM128065
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007183
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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