Stress-Specific Activation and Repression of Heat Shock Factors 1 and 2

Mathew, Anu; Mathur, Sameer K.; Jolly, Caroline; Fox, Susan G.; Kim, Soojin; Morimoto, Richard I.

doi:10.1128/mcb.21.21.7163-7171.2001

Cited by 113 publications

(87 citation statements)

References 70 publications

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“…During hemin treatment we observed binding of HSF1 and HSF2 to the hsp70 promoter (Fig. 1B), which is in line with previous studies (23,25,36,(45)(46)(47). To our surprise, HSF2 was found on the hsp70 promoter also upon heat shock (Fig.…”

Section: Both Hsf1 and Hsf2 Are Recruited To The Hsp70 Promoter-supporting

confidence: 81%

Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1

Östling

Björk

Roos-Mattjus

et al. 2007

Journal of Biological Chemistry

203

191

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The heat shock response is a defense reaction activated by proteotoxic damage induced by physiological or environmental stress. Cells respond to the proteotoxic damage by elevated expression of heat shock proteins (Hsps) that function as molecular chaperones and maintain the vital homeostasis of protein folds. Heat shock factors (HSFs) are the main transcriptional regulators of the stress-induced expression of hsp genes. Mammalian HSF1 was originally identified as the transcriptional regulator of the heat shock response, whereas HSF2 has not been implicated a role in the stress response. Previously, we and others have demonstrated that HSF1 and HSF2 interact through their trimerization domains, but the functional consequence of this interaction remained unclear. We have now demonstrated on chromatin that both HSF1 and HSF2 were able to bind the hsp70 promoter not only in response to heat shock but also during hemin-induced differentiation of K562 erythroleukemia cells. In both cases an intact HSF1 was required in order to reach maximal levels of promoter occupancy, suggesting that HSF1 influences the DNA binding activity of HSF2. The functional consequence of the HSF1-HSF2 interplay was demonstrated by real-time reverse transcription-PCR analyses, which showed that HSF2 was able to modulate the HSF1-mediated expression of major hsp genes. Our results reveal, contrary to the predominant model, that HSF2 indeed participates in the transcriptional regulation of the heat shock response.The heat shock response enables the cell to cope with the deleterious effects of protein-damaging stresses, e.g. heat, heavy metals, and viral and bacterial infections. Characteristic of the heat shock response is a down-regulation of gene transcription and protein synthesis in general, whereas the transcription of a specific subset of genes called the heat shock genes is induced (1, 2). The classical heat shock genes include the hsp genes, but genome-wide analysis has revealed numerous other genes to be activated by heat and other stresses (3). During heat shock, the Hsps 3 function as molecular chaperones that bind to and aid the folding of damaged proteins, thereby preventing protein aggregation under stressful conditions (1, 4, 5). The induction of Hsps is mainly regulated by a family of heat shock transcription factors (HSFs), which bind to the heat shock elements (HSEs) on heat shock genes and other target genes (6 -9).Four HSFs (HSF1-4) exist in vertebrates. HSF1 and HSF2 are the most studied factors because of their co-expression in most tissues and cell lines (9). HSF3 has been found only in avian species, and HSF4 is the most recently identified member in mammals and expressed predominantly in lens and brain (10 -15). Mammalian HSF1 corresponds to the single HSF in yeast, nematode, and fruit fly (16 -19) and is considered the bona fide stress-activated transcription factor. Mice lacking HSF1 and fibroblasts derived from these animals are sensitive to stress and do not develop thermotolerance or display induction of Hsps upo...

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Section: Both Hsf1 and Hsf2 Are Recruited To The Hsp70 Promoter-supporting

confidence: 81%

Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1

Östling

Björk

Roos-Mattjus

et al. 2007

Journal of Biological Chemistry

203

191

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“…HSF1 protein produced in reticulocyte lysates is active for DNA binding, provided that the extracts have first been heated. In contrast, HSF2 protein shows a constitutive HSE-binding activity but loses this activity upon heat treatment [3,32]. Therefore, it appeared that the DNA-binding activity of HSF2 protein was much more sensitive than that of HSF1 protein, at least when synthesized in vitro.…”

Section: R E S U L T Smentioning

confidence: 90%

“…P2 (10 ng) was end-labeled with [c- 32 Individual Sel6 clones were sequenced using the T7 sequencing kit from Pharmacia Biotech and the T7 primer according to the manufacturer's instructions.…”

Section: Sequencing Of the Products Of Selectionmentioning

confidence: 99%

Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

Manuel¹,

Rallu²,

Loones³

et al. 2002

European Journal of Biochemistry

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Heat shock transcription factors (HSFs) are characterized by their ability, upon activation, to bind to heat shock response elements (HSE) present in the promoter of their target genes. HSE are composed of inverted repeats of the pentamer nGAAm. In this study, we compare the embryonic HSF2 protein, purified from F9 embryonal carcinoma cells tumor, and the in vitro synthesized HSF2. We show that the context of HSF2 synthesis influences its thermosensitivity and DNA-binding properties. Therefore, we determined the consensus binding sequence for the purified embryonic HSF2 by the technique of systematic evolution of ligands by exponential enrichment (SELEX). We show that embryonic HSF2 prefers sites containing three or four nGAAm inverted pentamers and that its optimal binding sequence contains the 8-mer palindromic core 5¢-TTCTAGAA-3¢. The consensus binding sequence for the embryonic HSF2 will be very helpful to identify new targets for this factor, during developmental and differentiation processes.Keywords: heat shock transcription factor-2; protein purification; cooperativity; SELEX; consensus binding sequence.Heat shock factor 2 (HSF2) belongs to the vertebrate heat shock factor family that also includes HSF1, HSF3 and HSF4 [1][2][3][4][5]. The members of the HSF family are defined by their ability to specifically bind the regulatory sequence heat shock element (HSE) [6]. Located in the regulatory regions of heat shock genes, HSE consists of the inverted repeat of a basal element nGAAm [7]. Two inverted repeats are sufficient for Drosophila HSF binding, but optimal binding is obtained with three repeats [8]. In agreement with this observation, the activated form of HSFs has been demonstrated to be a trimer in yeast [9], in Drosophila [10], in human [11,12] or in mouse [13]. The HSE-binding activity of heat shock factors is not constitutive, but induced by various stresses, by differentiation or developmental processes. HSF1 and HSF3 are activated by stresses that elicit the so-called Ôheat shock responseÕ and induce the transcription of heat shock genes. HSF1 corresponds to the paradigm member of the family and is the functional homolog, for its function in the heat shock response, of the unique HSF found in yeast and Drosophila. Avian HSF3 is activated by more severe stresses than HSF1, but is also required for an optimal response to stress [14,15]. Indeed, avian cells expressing HSF1, but in which the HSF3 gene has been disrupted, exhibit a diminished response to stress, even at mild heat shock temperatures [14]. Athough heterotrimers were never detected, HSFs may interact with each other in a more complex way.HSF4 is an exception and constitutively binds DNA as a trimer in the absence of stress. Its expression is regulated in a tissue-specific manner [5,16]. The Hsf4 gene generates both an activator or a repressor of heat shock genes by alternative splicing; the tissue-specificity of the two forms may create a modulation of expression of hsps in the different tissues.In contrast to HSF1 and HSF3, HSF2 is no...

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“…Binding specificities of plant Hsfs to different Hsp promoters have not been much analyzed. In vertebrate cells, Hsps are thought to have a role in the positive regulation of Hsf2 (Mathew et al 2001). According to Bjork and Sistonen (2010), a negative feedback loop operates as evidenced by interactions between human Hsf1 and Hsps (such as Hsp70/Hsp40 and Hsp90) as well as by the fact that Hsps keep Hsf1 in an inactive form under non-stress conditions.…”

Section: Noted That the Induced Response To Hs Is Lost If The Canonicmentioning

confidence: 99%

OsHsfA2c and OsHsfB4b are involved in the transcriptional regulation of cytoplasmic OsClpB (Hsp100) gene in rice (Oryza sativa L.)

Singh

Mittal

Lavania

et al. 2012

Cell Stress and Chaperones

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ClpB-cytoplasmic (ClpB-cyt)/Hsp100 is an important chaperone protein in rice. Cellular expression of OsClpB-cyt transcript is governed by heat stress, metal stress, and developmental cues. Transgenic rice plants produced with 2 kb OsClpB-cyt promoter driving Gus reporter gene showed heat-and metal-regulated Gus expression in vegetative tissues and constitutive Gus expression in calli, flowering tissues, and embryonal half of seeds. Rice seedlings regenerated with OsClpB-cyt promoter fragment with deletion of its canonical heat shock element sequence (HSE −273 to −280 ) showed not only heat shock inducibility of Gus transcript/protein but also constitutive expression of Gus in vegetative tissues. It thus emerges that the only classical HSE present in OsClpB-cyt promoter is involved in repressing expression of OsClpB-cyt transcript under unstressed control conditions. Yeast onehybrid assays suggested that OsHsfA2c specifically interacts with OsClpB-cyt promoter. OsHsfA2c also showed binding with OsClpB-cyt and OsHsfB4b showed binding with OsClpB-cyt; notably, interaction of OsHsfB4b was seen for all three OsClpB/Hsp100 protein isoforms (i.e., ClpBcytoplasmic, ClpB-mitochondrial, and ClpB-chloroplastic).Furthermore, OsHsfB4b showed interaction with OsHsfA2c. This study suggests that OsHsfA2c may play a role as transcriptional activator and that OsHsfB4b is an important part of this heat shock responsive circuitry.

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Stress-Specific Activation and Repression of Heat Shock Factors 1 and 2

Cited by 113 publications

References 70 publications

Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1

Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1

Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

OsHsfA2c and OsHsfB4b are involved in the transcriptional regulation of cytoplasmic OsClpB (Hsp100) gene in rice (Oryza sativa L.)

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