Similar Datasets
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
| PRJNA862076 | 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:The heat shock response (HSR) is an ancient and highly conserved program of stress-induced gene expression, aimed at reestablishing protein homeostasis to preserve cellular fitness. Cells that fail to activate or maintain this protective response are hypersensitive to proteotoxic stress. The HSR is mediated by the heat shock transcription factor 1 (HSF1), which binds to conserved heat shock elements (HSE) in the promoter region of heat shock genes, resulting in the expression of heat shock proteins (HSP). Recently, we observed that hyperactivation of RhoA conditions cardiomyocytes for the cardiac arrhythmia atrial fibrillation. Also, the HSR is annihilated in atrial fibrillation, and induction of HSR mitigates sensitization of cells to this disease. Therefore, we hypothesized active RhoA to suppress the HSR resulting in sensitization of cells for proteotoxic stimuli.Stimulation of RhoA activity significantly suppressed the proteotoxic stress-induced HSR in HL-1 atrial cardiomyocytes as determined with a luciferase reporter construct driven by the HSF1 regulated human HSP70 (HSPA1A) promoter and HSP protein expression by Western Blot analysis. Inversely, RhoA inhibition boosted the proteotoxic stress-induced HSR. While active RhoA did not preclude HSF1 nuclear accumulation, phosphorylation, acetylation, or sumoylation, it did impair binding of HSF1 to the hsp genes promoter element HSE. Impaired binding results in suppression of HSP expression and sensitized cells to proteotoxic stress.These results reveal that active RhoA negatively regulates the HSR via attenuation of the HSF1-HSE binding and thus may play a role in sensitizing cells to proteotoxic stimuli.
| S-EPMC4508109 | biostudies-literature
Project description:At present, the barrier to HIV-1 functional cure is the persistence of HIV-1 reservoirs. The "shock (reversing latency) and kill (antiretroviral therapy)" strategy sheds light on reducing or eliminating the latent reservoir of HIV-1. However, the current limits of latency-reversing agents (LRAs) are their toxicity or side effects, which limit their practicability pharmacologically and immunologically. Our previous research found that HSF1 is a key transcriptional regulatory factor in the reversion of HIV-1 latency. We then constructed the in vitro HSF1-knockout (HSF1-KO) HIV-1 latency models and found that HSF1 depletion inhibited the reactivation ability of LRAs including salubrinal, carfizomib, bortezomib, PR-957 and resveratrol, respectively. Furthermore, bortezomib/carfizomib treatment induced the increase of heat shock elements (HSEs) activity after HSF1-KO, suggesting that HSEs participated in reversing the latent HIV-1. Subsequent investigation showed that latent HIV-1-reversal by H2O2-induced DNA damage was inhibited by PARP1 inhibitors, while PARP1 was unable to down-regulate HSF1-depleted HSE activity, indicating that PARP1 could serve as a replaceable protein for HSF1 in HIV-1 latent cells. In summary, we succeeded in finding the mechanisms by which HSF1 reactivates the latent HIV-1, which also provides a theoretical basis for the further development of LRAs that specifically target HSF1.
| S-EPMC9367301 | biostudies-literature
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