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Gene Review

Hsf  -  Heat shock factor

Drosophila melanogaster

Synonyms: CG5748, D-HSF, Dm-Hsf, DmHSF, DmHSFa, ...
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Disease relevance of Hsf

  • Drosophila HSF produced in E. coli under nonshock conditions forms a hexamer that binds specifically to DNA with high affinity and activates transcription from a heat shock promoter in vitro [1].
  • We have observed that, in Drosophila cells, the 14-3-3zeta is up-regulated under heat stress conditions, a process mediated by a heat shock transcription factor [2].

High impact information on Hsf

  • The binding of HSF to one of a pair of adjacent trimeric binding sites facilitates HSF binding to the second by over 2000-fold [3].
  • We have previously reported evidence that subunits of HSF associate to form homotrimers and that each subunit contacts a conserved 5 bp DNA sequence repeated within an HSE [3].
  • In contrast, when HSF is expressed in Xenopus oocytes, maximal DNA binding affinity is observed only after heat shock induction [1].
  • Such an enhancer can also be generated by duplication of HSE sequences from the Drosophila hsp70 promoter, which were previously identified as an upstream promoter element and are known to bind a purified heat shock transcription factor in vitro [4].
  • Footprint analysis of the HSTF on the hsp 70 gene reveals that it binds specifically to a 55 bp region upstream from the TATA box [5].

Biological context of Hsf

  • This cooperativity is particularly important in binding HSF at 37 degrees C, and could account for the requirement for multiple binding sites in vivo and, in part, for the differential expression of heat shock genes [3].
  • Our findings suggest that alternative splicing regulates the transcriptional activity of dHSF [6].
  • We conclude that HSF activation evolves rapidly during laboratory culture at diverse temperatures and could play an important role in the evolution of the heat-shock response [7].
  • We assayed HSF binding to various transgenic heat shock promoters in situ by measuring amounts of fluorescence at transgenic loci of polytene chromosomes that were stained with an HSF antibody [8].
  • After a 90-sec heat shock, we detect heat shock factor (HSF) at the transposon insertion sites; and after a 5-min shock its spatial distribution on the induced transgene puffs is clearly resolved from that of Pol II [9].

Anatomical context of Hsf

  • In the cytosol of nonshocked cells, the dHSF is present as a monomer that cannot bind DNA [10].
  • In normally growing Drosophila cultured cells the Drosophila heat shock transcription factor (dHSF) is localized in the cytosol and translocates into the nucleus after heat shock [10].
  • The induction of heat shock genes in eukaryotic cells is regulated by the transcription factor heat shock factor (HSF) [11].
  • Using cell-free systems for chromatin reconstitution and transcription, we have analyzed the mechanisms by which heat shock factor (HSF) increases transcription of heat shock genes in chromatin [12].
  • These data show that the expression and induction of the different small Hsps is regulated in a cell-specific manner under both normal and heat shock conditions and suggest that factors other than the DmHSF are involved in this regulation in male gonads [13].

Associations of Hsf with chemical compounds

  • Unlike the TAFs and Pol II, the interaction between Mediator and HSF on chromosomal loci is direct and mechanistically separable from the preinitiation complex assembly step [14].
  • The potential role of the HSTF and the B factor in the activation of heat-shock gene transcription is discussed [5].
  • Other inducers of the heat shock response, including salicylate, dinitrophenol, ethanol, and arsenite, have no effect on HSF trimerization in vitro, indicating that these inducers act by indirect mechanisms [15].
  • Heat shock transcription factor (HSF) is a multidomain protein that exists as a monomer under normal conditions and is reversibly induced upon heat shock to a trimeric state that binds to DNA with high affinity [16].

Other interactions of Hsf

  • Consistant with previous studies demonstrating that early Drosophila embryos are refractory to heat shock as a result of dHSF nuclear exclusion, we demonstrate that the early embryo is deficient in dKap-alpha3 protein through cycle 12 [17].
  • The heat shock transcriptional factor of Drosophila (DmHSF), present in significantly lower amount in testes when compared to other tissues such as the head, was shown to be required for the heat activation of Hsp22 and Hsp70 [13].
  • The cell-specific induction of Hsp23 under stress conditions does not seem to be regulated by the Drosophila melanogaster heat shock transcriptional factor (DmHSF) [18].

Analytical, diagnostic and therapeutic context of Hsf

  • At lower heat-shock temperatures (27-35 degrees C), flies from the 18 degrees C population had higher levels of activated HSF (as detected by an electrophoretic mobility shift assay) than those reared at 25 degrees C and 28 degrees C. At higher temperatures (36 and 37 degrees C), however, the 28 degrees C flies had the highest levels of HSF [7].
  • Using cDNA arrays in a genomic search for Hsf targets, we identified 141 genes with highly significant ChIP enrichment [19].
  • In this study, the oligomeric properties of Drosophila HSF were analyzed by equilibrium analytical ultracentrifugation and gel filtration chromatography [20].
  • Exchange broadening of the 15N-1H correlations upon titration of 15N labeled HSF with a 13-base-pair DNA duplex suggests a DNA-binding motif in which the third helix acts as the recognition helix [21].
  • Analyses of HSF association by indirect immunofluorescence with an anti-HSF antibody reveal that fluorescent signals at many loci on polytene chromosomes rapidly increase and then gradually decrease as heat shock time progresses [22].


  1. Molecular cloning and expression of a hexameric Drosophila heat shock factor subject to negative regulation. Clos, J., Westwood, J.T., Becker, P.B., Wilson, S., Lambert, K., Wu, C. Cell (1990) [Pubmed]
  2. A Novel Function of 14-3-3 Protein: 14-3-3{zeta} Is a Heat-Shock-related Molecular Chaperone That Dissolves Thermal-aggregated Proteins. Yano, M., Nakamuta, S., Wu, X., Okumura, Y., Kido, H. Mol. Biol. Cell (2006) [Pubmed]
  3. Cooperative binding of Drosophila heat shock factor to arrays of a conserved 5 bp unit. Xiao, H., Perisic, O., Lis, J.T. Cell (1991) [Pubmed]
  4. Heat shock regulatory elements function as an inducible enhancer in the Xenopus hsp70 gene and when linked to a heterologous promoter. Bienz, M., Pelham, H.R. Cell (1986) [Pubmed]
  5. A Drosophila RNA polymerase II transcription factor binds to the regulatory site of an hsp 70 gene. Parker, C.S., Topol, J. Cell (1984) [Pubmed]
  6. Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress. Fujikake, N., Nagai, Y., Popiel, H.A., Kano, H., Yamaguchi, M., Toda, T. FEBS Lett. (2005) [Pubmed]
  7. Laboratory selection at different temperatures modifies heat-shock transcription factor (HSF) activation in Drosophila melanogaster. Lerman, D.N., Feder, M.E. J. Exp. Biol. (2001) [Pubmed]
  8. HSF access to heat shock elements in vivo depends critically on promoter architecture defined by GAGA factor, TFIID, and RNA polymerase II binding sites. Shopland, L.S., Hirayoshi, K., Fernandes, M., Lis, J.T. Genes Dev. (1995) [Pubmed]
  9. Locus-specific variation in phosphorylation state of RNA polymerase II in vivo: correlations with gene activity and transcript processing. Weeks, J.R., Hardin, S.E., Shen, J., Lee, J.M., Greenleaf, A.L. Genes Dev. (1993) [Pubmed]
  10. Nuclear entry, oligomerization, and DNA binding of the Drosophila heat shock transcription factor are regulated by a unique nuclear localization sequence. Zandi, E., Tran, T.N., Chamberlain, W., Parker, C.S. Genes Dev. (1997) [Pubmed]
  11. Activation of Drosophila heat shock factor: conformational change associated with a monomer-to-trimer transition. Westwood, J.T., Wu, C. Mol. Cell. Biol. (1993) [Pubmed]
  12. Heat shock factor increases the reinitiation rate from potentiated chromatin templates. Sandaltzopoulos, R., Becker, P.B. Mol. Cell. Biol. (1998) [Pubmed]
  13. Cell-specific expression and heat-shock induction of Hsps during spermatogenesis in Drosophila melanogaster. Michaud, S., Marin, R., Westwood, J.T., Tanguay, R.M. J. Cell. Sci. (1997) [Pubmed]
  14. Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock. Park, J.M., Werner, J., Kim, J.M., Lis, J.T., Kim, Y.J. Mol. Cell (2001) [Pubmed]
  15. Direct sensing of heat and oxidation by Drosophila heat shock transcription factor. Zhong, M., Orosz, A., Wu, C. Mol. Cell (1998) [Pubmed]
  16. Regulation of Drosophila heat shock factor trimerization: global sequence requirements and independence of nuclear localization. Orosz, A., Wisniewski, J., Wu, C. Mol. Cell. Biol. (1996) [Pubmed]
  17. Developmental regulation of the heat shock response by nuclear transport factor karyopherin-alpha3. Fang, X., Chen, T., Tran, K., Parker, C.S. Development (2001) [Pubmed]
  18. Cell-specific heat-shock induction of Hsp23 in the eye of Drosophila melanogaster. Marin, R., Demers, M., Tanguay, R.M. Cell Stress Chaperones (1996) [Pubmed]
  19. Genomic analysis of heat-shock factor targets in Drosophila. Birch-Machin, I., Gao, S., Huen, D., McGirr, R., White, R.A., Russell, S. Genome Biol. (2005) [Pubmed]
  20. Sensitivity of Drosophila heat shock transcription factor to low pH. Zhong, M., Kim, S.J., Wu, C. J. Biol. Chem. (1999) [Pubmed]
  21. NMR evidence for similarities between the DNA-binding regions of Drosophila melanogaster heat shock factor and the helix-turn-helix and HNF-3/forkhead families of transcription factors. Vuister, G.W., Kim, S.J., Wu, C., Bax, A. Biochemistry (1994) [Pubmed]
  22. HSF recruitment and loss at most Drosophila heat shock loci is coordinated and depends on proximal promoter sequences. Shopland, L.S., Lis, J.T. Chromosoma (1996) [Pubmed]
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