Transcriptional regulation and binding of heat shock factor 1 and heat shock factor 2 to 32 human heat shock genes during thermal stress and differentiation

Trinklein, Nathan D.; Chen, Will C.; Kingston, Robert E.; Myers, R

doi:10.1379/481.1

Cited by 70 publications

(52 citation statements)

References 17 publications

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“…In fact, numerous evidence indicate that the mitochondrial genome is able to regulate a series of nuclear target genes by transcription factors, such as NFkB and CEBP, that acts as mediators of the well known cross-talk nucleusmitochondrion (Biswas et al 2005). The above hypothesis is also in line with literature data showing that promoters of HSP genes contain common and highly conserved binding sites for transcription factors some of which are specifically required for the heat shock response (Amin et al 1988;Trinklein et al 2004). We are currently investigating whether the above transcription factors are able to regulate also genes encoding for heat shock proteins localized in the cytoplasm and not only for those localized in the mitochondria.…”

Section: Discussionsupporting

confidence: 74%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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To explore possible relationships between mitochondrial DNA (mtDNA) polymorphism and the expression levels of stress-responder nuclear genes we assembled five cybrid cell lines by repopulating 143B.TK − cells, depleted of their own mtDNA (Rho 0 cells), with foreign mitochondria with different mtDNA sequences (lines H, J, T, U, X). We evaluated, at both basal and under heat stress conditions, gene expression (mRNA) and intra-mitochondrial protein levels of HSP60 and HSP75, two key components in cellular stress response. At basal conditions, the levels of HSP60 and HSP75 mRNA were lower in one cybrid (H) than in the others (p=0.005 and p=0.001, respectively). Under stress conditions, the H line over-expressed both genes, so that the inter-cybrid difference was abolished. Moreover, the HSP60 intra-mitochondrial protein levels differed among the cybrid lines (p=0.001), with levels higher in H than in the other cybrid lines. On the whole, our results provide further experimental evidence that mtDNA variability influences the cell response to stressful conditions by modulating components involved in this response. Sentence summary of the article: the results reported in the present study provide important experimental evidence that in human cells mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of genes involved in this response and their intra-mitochondrial protein levels.

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Section: Discussionsupporting

confidence: 74%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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“…(Trinklein et al 2004). To study the time and temperature dependence of HSF-1-dependent gene expression, we analyzed the effect of various levels of hyperthermia on activity of a reporter construct driven by a synthetic HSF-1-responsive reporter plasmid (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1D). These genes share heat-inducibility and heatactivated recruitment of HSF-1 to their promoter sequences (Trinklein et al 2004), suggesting the differential effects of the various heating protocols derives from variable temperature-dependent activation of HSF-1. HSF-1 is activated through a stepwise process comprising trimerization, nuclear translocation, and phosphorylation of serines in the transactivation domains (Cotto and Morimoto 1999).…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells

Tulapurkar

Asiegbu

Singh

et al. 2009

Cell Stress and Chaperones

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Expression of heat shock proteins (HSPs) is classically activated at temperatures above the physiologic range (≥42°C) via activation of the stress-activated transcription factor, heat shock factor-1 (HSF-1). Several studies suggest that less extreme hyperthermia, especially within the febrile range, as occurs during fever and exertional/environmental hyperthemia, can also activate HSF-1 and enhance HSP expression. We compared HSP72 protein and mRNA expression in human A549 lung epithelial cells continuously exposed to 38.5°C, 39.5°C, or 41°C or exposed to a classic heat shock (42°C for 2 h). We found that expression of HSP72 protein and mRNA increased linearly as incubation temperature was increased from 37°C to 41°C, but increased abruptly when the incubation temperature was raised to 42°C. A similar response in luciferase activity was observed using A549 cells stably transfected with an HSF-1-responsive luciferase reporter plasmid. However, activation of intranuclear HSF-1 DNA-binding activity was comparable at 38.5°C, 39.5°C, and 41°C and only modestly greater at 42°C but the mobility of HSF1 protein on a denaturing gel was altered with increasing exposure temperature and was distinctly different at 42°C. These findings indicate that the proportional changes in HSF-1-dependent HSP72 expression at febrile-range temperatures are dependent upon exposure time and temperature but not on the degree of HSF-1 DNA-binding activity. Instead, HSF-1-mediated HSP expression following hyperthermia and heat shock appears to be mediated, in addition to HSF-1 activation, by posttranslational modifications of HSF-1 protein.

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“…5) suggests that different HSFs may activate different downstream targets, leading to differential gene activity. HSF1 and HSF2 have been recently reported to activate various heat shock genes differentially (33). Differential binding of HSFs to HSEs in vitro has been reported (34,35).…”

Section: Fig 5 Hse-␣b/hsf Complexes Contain Hsf4mentioning

confidence: 99%

Developmentally Dictated Expression of Heat Shock Factors: Exclusive Expression of HSF4 in the Postnatal Lens and Its Specific Interaction with αB-crystallin Heat Shock Promoter

Somasundaram¹,

Bhat

2004

Journal of Biological Chemistry

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The molecular cascade of stress response in higher eukaryotes commences in the cytoplasm with the trimerization of the heat shock factor 1 (HSF1), followed by its transport to the nucleus, where it binds to the heat shock element leading to the activation of transcription from the down-stream gene(s). This well-established paradigm has been mostly studied in cultured cells. The developmental and tissue-specific control of the heat shock transcription factors (HSFs) and their interactions with heat shock promoters remain unexplored. We report here that in the rat lens, among the three mammalian HSFs, expression of HSF1 and HSF2 is largely fetal, whereas the expression of HSF4 is predominantly postnatal. Similar pattern of expression of HSF1 and HSF4 is seen in fetal and adult human lenses. This stagespecific inverse relationship between the expression of HSF1/2 and HSF4 suggests tissue-specific management of stress depending on the presence or absence of specific HSF(s). In addition to real-time PCR and immunoblotting, gel mobility shift assays, coupled with specific antibodies and HSE probes, derived from three different heat shock promoters, establish that there is no HSF1 or HSF2 binding activity in the postnatal lens nuclear extracts. Using this unique, developmentally modulated in vivo system, we demonstrate 1) specific patterns of HSF4 binding to heat shock elements derived from ␣B-crystallin, Hsp70, and Hsp82 promoters and 2) that it is HSF4 and not HSF1 or HSF2 that interacts with the canonical heat shock element of the ␣B-crystallin gene.Induced transcription from heat shock promoters is mediated by the activation of transacting HSFs 1 (1, 2). There are four known HSFs (HSF1, HSF2, HSF3, and HSF4). HSF3 is an avian HSF (3, 4). Although yeast and Drosophila melanogaster have a single gene that encodes an HSF, higher eukaryotes, animals, and plants have multiple genes that code for HSFs (4 -6). HSF1 and HSF2 transcription factors have almost identical gene structures (4). The heat shock response starts with the cytoplasmic HSF and its trimerization and transport to the nucleus, where it binds to the heat shock element (HSE) in the heat shock promoter, activating transcription of the down stream heat shock gene(s) (1, 4). Both HSF1 and HSF2 contain three hydrophobic repeats, HR-A, -B, and -C. HR-A and -B are involved in trimerization upon reception of the stress signal. HR-C, located at the carboxyl terminus, has been suggested to inhibit trimerization in the uninduced state. HSF4, on the other hand, does not contain the HR-C domain; it therefore exists as a trimeric unit and binds to the DNA constitutively (for review, see Ref. 4).HSF1 is considered to be the universal HSF and mediates expression of heat shock genes upon reception of a stress signal such as high temperature, whereas HSF2 is associated with developmental control. Although it has not been experimentally established, the assumption in this generalization is that all tissues and cells contain HSF1 as a pre-existing HSF in the cytoplasm to enab...

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Transcriptional regulation and binding of heat shock factor 1 and heat shock factor 2 to 32 human heat shock genes during thermal stress and differentiation

Cited by 70 publications

References 17 publications

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells

Developmentally Dictated Expression of Heat Shock Factors: Exclusive Expression of HSF4 in the Postnatal Lens and Its Specific Interaction with αB-crystallin Heat Shock Promoter

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