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Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
by
Xiang, Shengqi
, Zeng, Yong
, Wang, Xiaotian
, Shao, Shipeng
, Qin, Yizhi
, Xiao, Junyu
, Ren, Qiunan
, Sun, Yujie
, Wang, Yuxin
, Zhang, Hongchen
in
13/109
/ 14/32
/ 14/34
/ 14/35
/ 38/32
/ 38/91
/ 45/23
/ 631/337/470/1981
/ 631/337/572
/ 631/80/86/2366
/ 82/29
/ 82/80
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Condensates
/ Developmental Biology
/ Dispersion
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Gene loci
/ Heat shock
/ Heat shock factors
/ Heat shock proteins
/ Heat Shock Transcription Factors - genetics
/ Heat stress
/ Heat tolerance
/ Heat-Shock Proteins - metabolism
/ Heat-Shock Response - genetics
/ Homeostasis
/ HSF1 protein
/ HSP70 Heat-Shock Proteins - genetics
/ HSP70 Heat-Shock Proteins - metabolism
/ Hsp70 protein
/ Image resolution
/ Life Sciences
/ Liquid phases
/ Next-generation sequencing
/ Phase separation
/ Phase transitions
/ Phosphorylation
/ Proteins
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
2022
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Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
by
Xiang, Shengqi
, Zeng, Yong
, Wang, Xiaotian
, Shao, Shipeng
, Qin, Yizhi
, Xiao, Junyu
, Ren, Qiunan
, Sun, Yujie
, Wang, Yuxin
, Zhang, Hongchen
in
13/109
/ 14/32
/ 14/34
/ 14/35
/ 38/32
/ 38/91
/ 45/23
/ 631/337/470/1981
/ 631/337/572
/ 631/80/86/2366
/ 82/29
/ 82/80
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Condensates
/ Developmental Biology
/ Dispersion
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Gene loci
/ Heat shock
/ Heat shock factors
/ Heat shock proteins
/ Heat Shock Transcription Factors - genetics
/ Heat stress
/ Heat tolerance
/ Heat-Shock Proteins - metabolism
/ Heat-Shock Response - genetics
/ Homeostasis
/ HSF1 protein
/ HSP70 Heat-Shock Proteins - genetics
/ HSP70 Heat-Shock Proteins - metabolism
/ Hsp70 protein
/ Image resolution
/ Life Sciences
/ Liquid phases
/ Next-generation sequencing
/ Phase separation
/ Phase transitions
/ Phosphorylation
/ Proteins
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
2022
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Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
by
Xiang, Shengqi
, Zeng, Yong
, Wang, Xiaotian
, Shao, Shipeng
, Qin, Yizhi
, Xiao, Junyu
, Ren, Qiunan
, Sun, Yujie
, Wang, Yuxin
, Zhang, Hongchen
in
13/109
/ 14/32
/ 14/34
/ 14/35
/ 38/32
/ 38/91
/ 45/23
/ 631/337/470/1981
/ 631/337/572
/ 631/80/86/2366
/ 82/29
/ 82/80
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Condensates
/ Developmental Biology
/ Dispersion
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Gene loci
/ Heat shock
/ Heat shock factors
/ Heat shock proteins
/ Heat Shock Transcription Factors - genetics
/ Heat stress
/ Heat tolerance
/ Heat-Shock Proteins - metabolism
/ Heat-Shock Response - genetics
/ Homeostasis
/ HSF1 protein
/ HSP70 Heat-Shock Proteins - genetics
/ HSP70 Heat-Shock Proteins - metabolism
/ Hsp70 protein
/ Image resolution
/ Life Sciences
/ Liquid phases
/ Next-generation sequencing
/ Phase separation
/ Phase transitions
/ Phosphorylation
/ Proteins
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
2022
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Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
Journal Article
Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
2022
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Overview
Heat-shock transcription factor 1 (HSF1) orchestrates the fast and vast cellular response to heat shock through increased expression of heat-shock proteins. However, how HSF1 rapidly and reversibly regulates transcriptional reprogramming remains poorly defined. Here by combining super-resolution imaging, in vitro reconstitution and high-throughput sequencing, we reveal that HSF1 forms small nuclear condensates via liquid–liquid phase separation at heat-shock-protein gene loci and enriches multiple transcription apparatuses through co-phase separation to promote the transcription of target genes. Furthermore, the phase-separation capability of HSF1 is fine-tuned through phosphorylation at specific sites within the regulatory domain. Last, we discovered that HSP70 disperses HSF1 condensates to attenuate transcription following the cessation of heat shock and further prevents the gel-like phase transition of HSF1 under extended heat-shock stress. Our work reveals an inducible and reversible phase-separation feedback mechanism for dynamic regulation of HSF1 activity to drive the transcriptional response and maintain protein homeostasis during acute stress.
Zhang, Shao and coworkers report that HSF1 forms small condensates at its target gene loci to promote their transcription during acute heat stress. The produced HSP70 proteins in turn disperse HSF1 condensates to shut off the heat-shock response.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/32
/ 14/34
/ 14/35
/ 38/32
/ 38/91
/ 45/23
/ 82/29
/ 82/80
/ Biomedical and Life Sciences
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Heat Shock Transcription Factors - genetics
/ Heat-Shock Proteins - metabolism
/ Heat-Shock Response - genetics
/ HSP70 Heat-Shock Proteins - genetics
/ HSP70 Heat-Shock Proteins - metabolism
/ Proteins
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