Transcriptional changes to cytotoxic stresses are driven by HSF-activated genes and enhancers [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE183244 | GEO | 2022/06/10
REPOSITORIES: GEO
Similar Datasets
Project description:We utilized precicion run-on sequencing (PRO-seq) to analyze the roles of HSF1 and HSF2 in the reprogramming of transcription under oxidative stress and heat shock. PRO-seq was performed in wild-type (WT), HSF1 knock-out (HSF1 KO) and HSF2 knock-out (HSF2 KO) mouse embryonic fibroblasts (MEFs) that were treated with heat shock (HS) or oxidative stress induced by menadione (MD).
2022-06-10 | GSE183243 | GEO
Project description:Heat shock transcription factors HSF1 and HSF2 both are necessary for proper spermatogenesis, which is disrupted at elevated temperatures. We studied how HSF1 and HSF2 cooperate during the heat shock response in mouse spermatocytes. For this purpose we used ChIP-sequencing. ChIP-Seq analyses revealed that the temperature elevation induces remodeling of HSF1 and HSF2 binding to chromatin. The highest HSF1-chromatin binding was observed at 43°C, when HSF2-chromatin binding was reduced. Many promoters (mainly Hsp genes) were occupied by both heat shock factors at physiological temperature of testes and/or at 38°C. In contrary at 43°C only HSF1 was bound. Obtained results suggest that HSF1 and HSF2 could cooperate in regulation of the transcription of some genes only at physiological temperatures and/or at 38°C. Alteration in HSFs interactions and their binding to chromatin could be one of the reason of increased spermatogenic cell death observed after heat shock.
2014-10-07 | GSE56735 | GEO
Project description:Heat shock transcription factors HSF1 and HSF2 both are necessary for proper spermatogenesis, which is disrupted at elevated temperatures. We studied how HSF1 and HSF2 cooperate during the heat shock response in mouse spermatocytes. For this purpose we used ChIP-sequencing. ChIP-Seq analyses revealed that the temperature elevation induces remodeling of HSF1 and HSF2 binding to chromatin. The highest HSF1-chromatin binding was observed at 43M-BM-0C, when HSF2-chromatin binding was reduced. Many promoters (mainly Hsp genes) were occupied by both heat shock factors at physiological temperature of testes and/or at 38M-BM-0C. In contrary at 43M-BM-0C only HSF1 was bound. Obtained results suggest that HSF1 and HSF2 could cooperate in regulation of the transcription of some genes only at physiological temperatures and/or at 38M-BM-0C. Alteration in HSFs interactions and their binding to chromatin could be one of the reason of increased spermatogenic cell death observed after heat shock. On Illumina platform we sequenced DNA immunoprecipitated from isolated spermatocytes using anti-HSF1 antibody or anti-HSF2 antibody. Cells were either untreated (control) or heat shocked for 5-20 minutes. Two PCR-verified ChIP replicates were collected per each sample, and three negative control samples with normal goat serum were included.
2014-10-07 | E-GEOD-56735 | biostudies-arrayexpress
Project description:Heat shock factor 1 (HSF1) is well known for its role in the heat shock response (HSR), where it drives a transcriptional program comprising heat shock protein (HSP) genes, and in tumorigenesis, where it drives a program comprising HSPs and many non-canonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no significant role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have strikingly similar chromatin occupancy and regulate a common set of genes which include both HSPs and non-canonical transcriptional targets with roles critical in supporting malignancy. Loss of either HSF1 or HSF2 results in a dysregulated response to nutrient stresses in vitro and reduced tumor progression in cancer cell line xenografts. Taken together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.
2022-03-15 | GSE194098 | GEO
Project description:Genome-wide characterization of binding sites for heat shock transcription factors HSF1 and HSF2 in freely cycling and mitotic K562 cells in optimal growth conditions and upon 30 min heat stress at 42C
2013-08-04 | GSE43579 | GEO
Project description:RNA sequencing (RNA-seq) was used to study the impact of heat shock factors 1 and 2 (HSF1 and HSF2) on gene expression in normal growth conditions, upon Bortezomib-induced proteasome inhibition (25 nM, 6 h or 10 h), and upon heat shock (42∘C, 1 h).
2020-01-14 | GSE115973 | GEO
Project description:Investigation of whole genome gene expression level changes in oocytes Hsf1-/- or Hsf2-/- compared to wild-type. The mutants analyzed in this study are further described in McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ. 1998. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 273(13):7523-8 and in McMillan DR, Christians E, Forster M, Xiao X, Connell P, Plumier JC, Zuo X, Richardson J, Morgan S, Benjamin IJ. 2002. Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Mol Cell Biol. 22(22):8005-14. A microarray study using two technical replicates of total RNA recovered from wild-type fully-grown oocytes, Hsf1 mutant fully-grown oocytes and Hsf2 mutant fully-grown oocytes. Each microarray measures the expression level of 42,586 probe sets from Mus musculus with nine 60-mer probe pairs per gene.
2011-06-30 | E-GEOD-26240 | biostudies-arrayexpress
Project description:Prostate cancer (PrCa) is one of the most common malignancies in Western countries. However, the pathways that promote invasion, especially in late-stage castration-resistant PrCa (CRPC), are poorly understood. Heat shock factors (HSFs) are transcriptional regulators essential for cell survival upon proteotoxic stress, and HSF1 is also identified as a driver of oncogenesis. Here, our aim was to elucidate the molecular mechanisms that contribute to CRPC and invasion. In silico analyses showed that high HSF1 expression levels correlate with poor survival and high Gleason score in PrCa. In the same data set, HSF2, which has not previously been linked to cancer, displayed decreased expression. Using 3-dimensional (3D) organotypic PrCa cultures that spontaneously undergo an invasive conversion, opposite effects of HSF1 and HSF2 were observed; tumor spheroids lacking HSF1 grew slowly, were polarized and devoid of invasive structures, and depletion of HSF2 potentiated invasiveness. In the in vivo xenograft chorioallantoic membrane model, HSF1 silencing caused tumor regression and fibrosis, and knockdown of HSF2 generated large invasive tumors, verifying the results from the 3D-cultures. Gene expression profiling revealed enrichment of genes connected to translational control when either HSF1 or HSF2 was silenced. HSF1-specific targets were associated with progression of tumorigenesis, whereas HSF2 targets were involved in focal adhesion, critical for invasion. This study provides the first evidence for HSF2 functioning in cancer, i.e. as a tumor suppressor. Moreover, human PrCa tissue microarrays demonstrated increased nuclear HSF1 expression, which significantly correlated with high-grade Gleason score. Cytoplasmic HSF1 was detected in a subset of tumors and intriguingly, correlated with decreased disease-specific survival. This was most pronounced in intermediate Gleason score 7 tumors and in metastases. We propose the use of HSF1 as a biomarker to predict PrCa outcome, thus facilitating clinical decision-making and supporting individualized treatment choices. HSF1 and HSF2 siRNA transfection was performed in triplicates (biological replicates), for 5 and 8 days prior to harvesting total RNA; and compared to PC-3 cells transfected with scrambled control siRNAs for 5 and 8 days, respectively.
2013-12-23 | E-GEOD-48672 | biostudies-arrayexpress
Project description:We hypothesized that broad-scale expression profiling would provide insight into the regulatory pathways that control gene expression in response to stress, and potentially identify novel heat-responsive genes. HEp2 cells were heated at 37 to 43 °C for 60 min to gauge the heat shock response, using as a proxy inducible HSP-70 quantified by western blot analysis. Based on these results, microarray experiments were conducted at 37, 40, 41, 42 and 43°C (3 replicates/temperature x 5 groups = 15 U95Aver2 GeneChips). Using linear modeling, we compared the sets of microarrays at 40, 41, 42 and 43°C with the 37°C baseline temperature and took the union of the genes exhibiting differential gene expression signal to create two sets of “heat shock response” genes, each set reflecting either increased or decreased RNA abundance. Leveraging human and mouse orthologous alignments, we used the two lists of co-expressed genes to predict transcription factor binding sites in silico, including those for heat shock factor 1 (HSF1) and heat shock factor 2 (HSF2) transcription factors. We discovered HSF1 and HSF2 binding sites in 15 genes not previously associated with the heat shock response. We conclude that microarray experiments coupled with upstream promoter analysis can be used to identify novel genes that respond to heat shock. Additional experiments are required to validate these putative heat shock proteins and facilitate a deeper understanding of the mechanisms involved during the stress response. Keywords: stress response, temperature, human epithelial cells
2007-04-10 | GSE7458 | GEO
Project description:Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response
(HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular
chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms,
having stress-induced activation and feedback regulations with multiple partners, the HSR is still
incompletely understood. In this context, we propose a minimal molecular model for the gene
regulatory network of the HSR that reproduces quantitatively different heat shock experiments both
on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics
laws, is kept with a low dimensionality without altering the biological interpretation of the model
dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of
the network. Moreover, by a steady states analysis of the network, three different temperature stress
regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal
adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes
are consequences of the titration mechanism. The simplicity of the present model is of interest in
order to study detailed modelling of cross regulation between the HSR and other major genetic
networks like the cell cycle or the circadian clock.
Sivéry, A., Courtade, E., Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Physical biology, 13(6), 066008.
2022-01-25 | MODEL2201210001 | BioModels