Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding
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PROVIDER: PRJNA862076 | ENA |
REPOSITORIES: ENA
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Project description:Background. The Heat Shock Response (HSR) is an evolutionarily conserved mechanism that helps cells adapt to environmental stresses. Heat Shock Factor 1 (HSF1) is a master HSR transcription factor that is long known to bind at promoters of its target HSP genes to rapidly activate their transcription. However, recent genome-wide studies revealed HSF1 binding at thousands of sites outside of heat-shock responsive gene promoters, implying a broader role of HSF1 in HSR. Results. We asked how the widespread HSF1 binding is established and to what extent it may be related to transcription activation. To answer these questions, we examined responses of two different human cancer cell lines to two stimuli that induce HSR, exposure to 42C and inorganic arsenic at the ambient temperature, by manually integrating ChIP-sequencing against HSF1, RNA Pol II, H3K4Me3 with nascent RNA- and ATAC-sequencing datasets in cells before and during HSR induced by these two stimuli. We show that widespread HSF1 binding is a temperature-agnostic hallmark of HSR whose genome-wide patterns combine cell type specificity with robustness to the nature of a stimulus and magnitude of activation. Mechanistically, HSR involves amplification of pre-existing low level HSF1 binding with few changes in accessible chromatin. HSF1 binding patterns show more stability than transcriptionally activated genes both between conditions and between cell lines. Conclusions. Comparing responses of distant cell lines to two HSR-inducing stimuli allowed us to define several features of HSR. Genome-wide HSF1 binding is a sensitive readout of HSR whose genome-wide patterns retain cell type identity across a broad dynamic range. The pre-existing genomic architecture is retained during HSR down to individual loci. Context-specific transcription involving common HSF1 binding favors a model of regulation by combinatory interplay of rigid transcription factor patterns.
2023-10-30 | GSE209685 | GEO
Project description:Background. The Heat Shock Response (HSR) is an evolutionarily conserved mechanism that helps cells adapt to environmental stresses. Heat Shock Factor 1 (HSF1) is a master HSR transcription factor that is long known to bind at promoters of its target HSP genes to rapidly activate their transcription. However, recent genome-wide studies revealed HSF1 binding at thousands of sites outside of heat-shock responsive gene promoters, implying a broader role of HSF1 in HSR. Results. We asked how the widespread HSF1 binding is established and to what extent it may be related to transcription activation. To answer these questions, we examined responses of two different human cancer cell lines to two stimuli that induce HSR, exposure to 42C and inorganic arsenic at the ambient temperature, by manually integrating ChIP-sequencing against HSF1, RNA Pol II, H3K4Me3 with nascent RNA- and ATAC-sequencing datasets in cells before and during HSR induced by these two stimuli. We show that widespread HSF1 binding is a temperature-agnostic hallmark of HSR whose genome-wide patterns combine cell type specificity with robustness to the nature of a stimulus and magnitude of activation. Mechanistically, HSR involves amplification of pre-existing low level HSF1 binding with few changes in accessible chromatin. HSF1 binding patterns show more stability than transcriptionally activated genes both between conditions and between cell lines. Conclusions. Comparing responses of distant cell lines to two HSR-inducing stimuli allowed us to define several features of HSR. Genome-wide HSF1 binding is a sensitive readout of HSR whose genome-wide patterns retain cell type identity across a broad dynamic range. The pre-existing genomic architecture is retained during HSR down to individual loci. Context-specific transcription involving common HSF1 binding favors a model of regulation by combinatory interplay of rigid transcription factor patterns.
2023-10-30 | GSE209675 | GEO
Project description:Background. The Heat Shock Response (HSR) is an evolutionarily conserved mechanism that helps cells adapt to environmental stresses. Heat Shock Factor 1 (HSF1) is a master HSR transcription factor that is long known to bind at promoters of its target HSP genes to rapidly activate their transcription. However, recent genome-wide studies revealed HSF1 binding at thousands of sites outside of heat-shock responsive gene promoters, implying a broader role of HSF1 in HSR. Results. We asked how the widespread HSF1 binding is established and to what extent it may be related to transcription activation. To answer these questions, we examined responses of two different human cancer cell lines to two stimuli that induce HSR, exposure to 42C and inorganic arsenic at the ambient temperature, by manually integrating ChIP-sequencing against HSF1, RNA Pol II, H3K4Me3 with nascent RNA- and ATAC-sequencing datasets in cells before and during HSR induced by these two stimuli. We show that widespread HSF1 binding is a temperature-agnostic hallmark of HSR whose genome-wide patterns combine cell type specificity with robustness to the nature of a stimulus and magnitude of activation. Mechanistically, HSR involves amplification of pre-existing low level HSF1 binding with few changes in accessible chromatin. HSF1 binding patterns show more stability than transcriptionally activated genes both between conditions and between cell lines. Conclusions. Comparing responses of distant cell lines to two HSR-inducing stimuli allowed us to define several features of HSR. Genome-wide HSF1 binding is a sensitive readout of HSR whose genome-wide patterns retain cell type identity across a broad dynamic range. The pre-existing genomic architecture is retained during HSR down to individual loci. Context-specific transcription involving common HSF1 binding favors a model of regulation by combinatory interplay of rigid transcription factor patterns.
2023-10-30 | GSE209667 | GEO
Project description:Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding
| PRJNA862089 | ENA
Project description:Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding
| PRJNA862105 | ENA
Project description:Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding
| PRJNA862114 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-30 | GSE209687 | GEO
Project description:Mouse HSF1+/+ and HSF1-/- Fibroblasts Heat Shock Time Courses Scanned on Scanner 7 (Axon 4000B) Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2005-08-05 | GSE3074 | GEO
Project description:Mouse HSF1+/+ and HSF1-/- Fibroblasts Heat Shock Time Courses Scanned on Scanner 7 (Axon 4000B)
2005-07-21 | E-SMDB-1853 | biostudies-arrayexpress
Project description:HSF1 binds DNA via the DBD domain, causing gene upregulation during HS. We assessed the effect of RD-mediated phase separation on chromatin targeting of HSF1 using Cut&Tag followed by high-throughput sequencing to map genome-wide binding of LLPS-competent versus LLPS-incompetent HSF1 mutants under both HS and NHS conditions. Comparing with WT HSF1 under NHS, both WT under HS and M1 under NHS showed increased and broad binding to enhancers and distal intergenic region, with binding most enriched in expected motifs of HSF-related transcription factors. To further assess the role for IDR-induced LLPS in chromatin targeting of HSF1, we used several additional strategies. First, the treatment of 1,6-hexanediol markedly decreased chromatin occupancy both of WT under HS and M1 under NHS conditions. Second, we interrogate chromatin binding of LLPS-deficient mutant M3. Cut&Tag analysis revealed that M3 showed decreased chromatin binding compared to WT under HS and M1 under NHS. The decreased chromatin binding of M3 to chromatin was not due to the loss of its DNA binding ability, as the EMSA assay revealed that M3 was still capable of binding HSE. Instead, the decreased chromatin binding reflects the loss of inter-molecular interaction between HSF1 that holds LLPS. Furthermore, M3 in heat shocked cells shows similar reduced genomic targeting and shallow binding pattern as NHS cells . Third, the enrichment of transcriptional apparatus RNA Pol II, CYCT1, BRD4 to HSF1 target genes also depend on whether HSF1 can phase separate at these sites. Lastly, we conducted live cell single molecule imaging to evaluate chromatin binding kinetics of LLPS-deficient mutant M3 relative to WT HSF1. Measurements of single molecule displacement and diffusion coefficient showed M3 to be significantly more mobile than WT under HS, which suggests M3 was less confined within phase-separated puncta compared with LLPS-competent HSF1. Consistent with this result, super resolution imaging of M3 also showed decreased cluster formation at HSP gene foci but maintained nSBs formation. Altogether, LLPS-forming capability of HSF1 is essential for the efficient recruitment of HSF1 and transcriptional apparatus to HSP gene loci.
2021-12-24 | GSE192370 | GEO