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HSF1 in the Yeast Saccharomyces Cerevisiaeã

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HSF1 in the Yeast Saccharomyces Cerevisiaeã Mol Gen Genet (1997) 255:322±331 Ó Springer-Verlag 1997 ORIGINAL PAPER O. Boscheinen á R. Lyck á C. Queitsch á E. Treuter V. Zimarino á K.-D. Scharf Heat stress transcription factors from tomato can functionally replace HSF1 in the yeast Saccharomyces cerevisiaeà Received: 1 October 1996 / Accepted: 6 December 1996 Abstract The fact that yeast HSF1 is essential for sur- nomeric Hsf has a markedly reduced anity for DNA, as vival under nonstress conditions can be used to test shown by lacZ reporter and band-shift assays. heterologous Hsfs for the ability to substitute for the endogenous protein. Our results demonstrate that like Key words Tomato á Yeast á Heat stress á Transcription Hsf of Drosophila, tomato Hsfs A1 and A2 can func- factor á Thermotolerance tionally replace the corresponding yeast protein, but Hsf B1 cannot. In addition to survival at 28° C, we checked the transformed yeast strains for temperature sensitivity Introduction of growth, induced thermotolerance and activator func- tion using two dierent lacZ reporter constructs. Tests The striking conservation of essential elements of the with full-length Hsfs were supplemented by assays using heat stress response is well documented by the 11 heat mutant Hsfs lacking parts of their C-terminal activator stress protein (Hsp) families, with representatives found region or oligomerization domain, or containing amino in all organisms investigated so far. As molecular acid substitutions in the DNA-binding domain. Re- chaperones, they form part of a homeostatic network markably, results with the yeast system are basically responsible for the proper folding, assembly, intracellu- similar to those obtained by the analysis of the same Hsfs lar distribution and degradation of proteins (see sum- as transcriptional activators in a tobacco protoplast as- maries by Nover 1991; Buchner 1996; Hartl 1996; say. Most surprising is the failure of HsfB1 to substitute Waters et al. 1996; Nover and Scharf 1997). Following for the yeast Hsf. The defect can be overcome by addition the initial identi®cation of the recognition element in the to HsfB1 of a short C-terminal peptide motif from HsfA2 promoters of Drosophila heat stress genes (Pelham and (34 amino acid residues), which represents a type of Bienz 1982), it soon became apparent that the conser- minimal activator necessary for interaction with the yeast vation also extends to heat stress elements (HSEs) in transcription apparatus. Deletion of the oligomerization other organisms, which show the basic structure of two domain (HR-A/B) does not interfere with Hsf function palindromic 5 bp modules in repetitive arrangements for survival or growth at higher temperatures. But mo- (-AGAAnnTTCT-). They are found upstream of the TATA box in all eukaryotic heat stress-inducible genes (Nover 1987, 1991). The long search for the putative regulatory proteins (Hsfs) binding to the HSE led to the Communicated by R. Herrmann isolation of the yeast HSF gene (Sorger and Pelham O. Boscheinen á R. Lyck á K.-D. Scharf (&) 1988; Wiederrecht et al. 1988) and subsequently to the Molecular Cell Biology, Biocenter of the J.W. Goethe University, corresponding cDNA clones from Drosophila (Clos et al. Marie-Curie-Str. 9, D-60439 Frankfurt, Germany Tel.: +49-69-798-29285; Fax: +49-69-798-29286 1990) and tomato (Lycopersicon peruvianum) (Scharf e-mail: [email protected] et al. 1990, 1993). A surprising peculiarity of the plant system was the identi®cation of three Hsf clones. Two O. Boscheinen á C. Queitsch á E. Treuter á K.-D. Scharf Institute of Plant Biochemistry, Weinberg 3, represented heat stress-inducible genes themselves, and D-06120 Halle, Germany this unique trait was also found in other plants (HuÈ bel V. Zimarino and SchoÈ 1994; Czarnecka-Verner et al. 1995; Gag- Biol. Technol. Res. Dept., San Raaele Sci. Institute, liardi et al. 1995). Via Olgettina 58, I-20132 Milan, Italy More than 25 Hsfs have been cloned and sequenced * Dedicated to Prof. B. Parthier (Halle) on the occasion of his 65th from dierent plants, vertebrates, Xenopus, and yeasts birthday (Nover et al. 1996). All proteins of this Hsf family have a 323 number of common features, which are summarized in motif from the C-terminus of HsfA2. The collection of Fig. 1 and Table 2. An N-terminal DNA-binding do- yeast strains described in this paper is a valuable tool for main contains a central helix-turn-helix motif involved analysis of Hsf function and for screening of interacting in DNA recognition (Harrison et al. 1994; Vuister et al. proteins. 1994; Schultheiss et al. 1996). The C-terminal region includes an oligomerization domain with a characteristic heptad repeat pattern of large hydrophobic amino acid Materials and methods residues (HR-A/B region), a nuclear localization signal (NLS, Lyck et al. 1997) and the C-terminal activator Yeast strains and culture media region (Treuter et al. 1993). Haploid strain RSY4 of Saccharomyces cerevisiae used for func- Considering the conservation of essential functional tional Hsf substitutions was derived from strain RSY10 (MATa/ parts of eukaryotic Hsfs (Scharf et al. 1994; Wu 1995; MATa, ade2/ade2, ade6, can1/can1, his3,11,15/his3,11,15, leu2-3, Nover et al. 1996) and the reports that the yeast HSF 112/leu2-3,112, trp1-1/trp1-1, ura3-1/ura3-1), a kind gift of Mark Vidal (Northwestern University, Evanston, Io.). Growth and gene is indispensable for survival and growth even at transformation of yeast strains and selection on 5-¯uoro-orotic 28° C (Sorger and Pelham 1988; Wiederrecht et al. 1988), acid (FOA) followed standard protocols (Ausubel et al. 1993; Rose we initiated investigations of the function of heterolo- et al. 1990). For chromosomal disruption of the HSF1 gene (Wi- gous Hsfs in yeast. In this paper, we demonstrate (i) that ederrecht et al. 1988) the parental strain was transformed with a derivative of pRS303(HIS3) containing Sc-HSF1 3¢ (EcoRV-XhoI, the Drosophila Hsf and the tomato Hsfs A1 and A2 are 2772-3676) and 5¢ (EcoRI-BamHI, 1-991) fragments, inserted in able to replace the yeast Hsf; (ii) that, at least for the tandem but reverse order in the KS polylinker. Prior to yeast tomato Hsfs A1 and A2, the structural requirements for transformation, plasmid DNA was linearized with EcoRI to re- activity in yeast are very similar to those found in to- move a short polylinker segment separating the two inserts. Inte- bacco protoplasts (Treuter et al. 1993); and (iii) that the gration at the HSF locus results in excision of 71.4% of the coding region. The remaining 5¢ sequences up to position 991, encoding the lack of function of a third tomato Hsf, B1, in the yeast 66 N-terminal amino acids of Sc-Hsf1, are insucient for yeast system can be overcome by adding a short activator viability (Sorger 1990). Fig. 1 Basic structure of Hsfs. Structure of the endogenous yeast Hsf residues. The C-terminal part contains the nuclear localization signal (Sc-Hsf1) is compared with those of Drosophila (Dm-Hsf) and of the (NLS), an additional heptad hydrophobic repeat region (HR-C)and three tomato Hsfs (Lp-HsfA1, A2 and B1). The N-terminal DNA- activator motifs (AHA1, AHA2) close to the HR-C region. The boxed binding domain (DBD) is separated from the C-terminal activator numbers below the block diagrams of the tomato Hsfs indicate domain by an oligomerization domain (HR-A/B). Note that in Lp- positions of restriction sites introduced for generation of the deletion Hsfs A1 and A2 the latter is extended by an insert of 21 amino acid and/or fusion constructs (see Table 1 and Materials and methods) 324 Plasmid constructions were raised in rabbits against recombinant (His)6-tagged Lp-Hsfs as antigens (Scharf et al. unpublished). Strain DH5a of Escherichia coli (F) /80d, lacZDM15 endA1 recA1 ) + ) hsdR17 (rK mK ) supE44 thi-1d gyrA96 D(lacZYA-argE)U169) was used for cloning and propagation of all shuttle vectors. Stan- b-Galactosidase assay dard procedures were used for cloning (Sambrook et al. 1989) and sequencing (Sanger et al. 1977). To assay the transcriptional activity of heterologous Hsf in Sc-Hsf The Dm-HSF cDNA, a 2.5 kb EcoRI fragment containing the substitution strains after FOA treatment, cells were transformed coding region and 5¢ (21 bp) and 3¢ (473 bp) untranslated se- with reporter plasmids pZJHSE2-137 (Slater and Craig 1987), quences inserted in pBluescript KS+ (Clos et al. 1990) was excised kindly provided by E. Craig, or pHSE2-BG (Sorger and Pelham with HindIII and NotI and directionally inserted in the yeast ex- 1987), kindly provided by P. Sorger. Both plasmids contain HSEs pression vector pADNS (2l, LEU2 based) (Colicelli et al. 1989) upstream of a truncated CYC1 promoter fused to the lacZ reporter between the ADH1 gene promoter and terminator. The related gene (see Fig. 6). The b-galactosidase assay was carried out as vector pAD4D (Ballester et al. 1989) was used for subcloning a described by Ellwood and Craig (1984) and Bonner et al. (1992). PvuII-EcoRI (EcoRI ®lled-in) fragment containing the coding re- gion of Sc-HSF1 (Wiederrecht et al. 1988) into the SmaI site of the vector. This vector was also used for expression of the wild-type Cross-linking forms and all C-terminal deletions of the tomato Hsfs. The corre- sponding DNA fragments were obtained as XhoI-XbaI(XbaI ®lled- Native protein extracts were prepared as described above, diluted in) fragments from the plant expression vectors described by in buer H to approximately 0.5 mg/ml total protein and adjusted Treuter et al. (1993), and subcloned into pAD4D digested with SalI to 150 mM NaCl.
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