Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells (original) (raw)

Abstract

Hemin induces nonterminal differentiation of human K562 erythroleukemia cells, which is accompanied by the expression of certain erythroid cell-specific genes, such as the embryonic and fetal globins, and elevated expression of the stress genes hsp70, hsp90, and grp78/BiP. Previous studies revealed that, as during heat shock, transcriptional induction of hsp70 in hemin-treated cells is mediated by activation of heat shock transcription factor (HSF), which binds to the heat shock element (HSE). We report here that hemin activates the DNA-binding activity of HSF2, whereas heat shock induces predominantly the DNA-binding activity of a distinct factor, HSF1. This constitutes the first example of HSF2 activation in vivo. Both hemin and heat shock treatments resulted in equivalent levels of HSF-HSE complexes as analyzed in vitro by gel mobility shift assay, yet transcription of the hsp70 gene was stimulated much less by hemin-induced HSF than by heat shock-induced HSF. Genomic footprinting experiments revealed that hemin-induced HSF and heat shock-induced HSF, HSF2, and HSF1, respectively, occupy the HSE of the human hsp70 promoter in a similar yet not identical manner. We speculate that the difference in occupancy and/or in the transcriptional abilities of HSF1 and HSF2 accounts for the observed differences in the stimulation of hsp70 gene transcription.

4104

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abravaya K., Phillips B., Morimoto R. I. Attenuation of the heat shock response in HeLa cells is mediated by the release of bound heat shock transcription factor and is modulated by changes in growth and in heat shock temperatures. Genes Dev. 1991 Nov;5(11):2117–2127. doi: 10.1101/gad.5.11.2117. [DOI] [PubMed] [Google Scholar]
  2. Abravaya K., Phillips B., Morimoto R. I. Heat shock-induced interactions of heat shock transcription factor and the human hsp70 promoter examined by in vivo footprinting. Mol Cell Biol. 1991 Jan;11(1):586–592. doi: 10.1128/mcb.11.1.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amici C., Sistonen L., Santoro M. G., Morimoto R. I. Antiproliferative prostaglandins activate heat shock transcription factor. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6227–6231. doi: 10.1073/pnas.89.14.6227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Amin J., Ananthan J., Voellmy R. Key features of heat shock regulatory elements. Mol Cell Biol. 1988 Sep;8(9):3761–3769. doi: 10.1128/mcb.8.9.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Banerji S. S., Laing K., Morimoto R. I. Erythroid lineage-specific expression and inducibility of the major heat shock protein HSP70 during avian embryogenesis. Genes Dev. 1987 Nov;1(9):946–953. doi: 10.1101/gad.1.9.946. [DOI] [PubMed] [Google Scholar]
  6. Banerji S. S., Theodorakis N. G., Morimoto R. I. Heat shock-induced translational control of HSP70 and globin synthesis in chicken reticulocytes. Mol Cell Biol. 1984 Nov;4(11):2437–2448. doi: 10.1128/mcb.4.11.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Becker P. B., Rabindran S. K., Wu C. Heat shock-regulated transcription in vitro from a reconstituted chromatin template. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4109–4113. doi: 10.1073/pnas.88.10.4109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chao M. V., Mellon P., Charnay P., Maniatis T., Axel R. The regulated expression of beta-globin genes introduced into mouse erythroleukemia cells. Cell. 1983 Feb;32(2):483–493. doi: 10.1016/0092-8674(83)90468-3. [DOI] [PubMed] [Google Scholar]
  9. Charnay P., Maniatis T. Transcriptional regulation of globin gene expression in the human erythroid cell line K562. Science. 1983 Jun 17;220(4603):1281–1283. doi: 10.1126/science.6574602. [DOI] [PubMed] [Google Scholar]
  10. Craig E. A., Gross C. A. Is hsp70 the cellular thermometer? Trends Biochem Sci. 1991 Apr;16(4):135–140. doi: 10.1016/0968-0004(91)90055-z. [DOI] [PubMed] [Google Scholar]
  11. Dean A., Erard F., Schneider A. P., Schechter A. N. Induction of hemoglobin accumulation in human K562 cells by hemin is reversible. Science. 1981 Apr 24;212(4493):459–461. doi: 10.1126/science.6163216. [DOI] [PubMed] [Google Scholar]
  12. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hickey E., Brandon S. E., Smale G., Lloyd D., Weber L. A. Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol Cell Biol. 1989 Jun;9(6):2615–2626. doi: 10.1128/mcb.9.6.2615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hightower L. E. Heat shock, stress proteins, chaperones, and proteotoxicity. Cell. 1991 Jul 26;66(2):191–197. doi: 10.1016/0092-8674(91)90611-2. [DOI] [PubMed] [Google Scholar]
  15. Jurivich D. A., Sistonen L., Kroes R. A., Morimoto R. I. Effect of sodium salicylate on the human heat shock response. Science. 1992 Mar 6;255(5049):1243–1245. doi: 10.1126/science.1546322. [DOI] [PubMed] [Google Scholar]
  16. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  17. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  18. Mezger V., Legagneux V., Babinet C., Morange M., Bensaude O. Heat shock protein synthesis in preimplantation mouse embryos and embryonal carcinoma cells. Results Probl Cell Differ. 1991;17:153–166. doi: 10.1007/978-3-540-46712-0_11. [DOI] [PubMed] [Google Scholar]
  19. Morgan W. D., Williams G. T., Morimoto R. I., Greene J., Kingston R. E., Tjian R. Two transcriptional activators, CCAAT-box-binding transcription factor and heat shock transcription factor, interact with a human hsp70 gene promoter. Mol Cell Biol. 1987 Mar;7(3):1129–1138. doi: 10.1128/mcb.7.3.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mosser D. D., Theodorakis N. G., Morimoto R. I. Coordinate changes in heat shock element-binding activity and HSP70 gene transcription rates in human cells. Mol Cell Biol. 1988 Nov;8(11):4736–4744. doi: 10.1128/mcb.8.11.4736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mueller P. R., Wold B. In vivo footprinting of a muscle specific enhancer by ligation mediated PCR. Science. 1989 Nov 10;246(4931):780–786. doi: 10.1126/science.2814500. [DOI] [PubMed] [Google Scholar]
  22. Ochoa S., de Haro C. Regulation of protein synthesis in eukaryotes. Annu Rev Biochem. 1979;48:549–580. doi: 10.1146/annurev.bi.48.070179.003001. [DOI] [PubMed] [Google Scholar]
  23. Padmanaban G., Venkateswar V., Rangarajan P. N. Haem as a multifunctional regulator. Trends Biochem Sci. 1989 Dec;14(12):492–496. doi: 10.1016/0968-0004(89)90182-5. [DOI] [PubMed] [Google Scholar]
  24. Pelham H. R. A regulatory upstream promoter element in the Drosophila hsp 70 heat-shock gene. Cell. 1982 Sep;30(2):517–528. doi: 10.1016/0092-8674(82)90249-5. [DOI] [PubMed] [Google Scholar]
  25. Phillips B., Morimoto R. I. Transcriptional regulation of human hsp70 genes: relationship between cell growth, differentiation, virus infection, and the stress response. Results Probl Cell Differ. 1991;17:167–187. doi: 10.1007/978-3-540-46712-0_12. [DOI] [PubMed] [Google Scholar]
  26. Rabindran S. K., Giorgi G., Clos J., Wu C. Molecular cloning and expression of a human heat shock factor, HSF1. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6906–6910. doi: 10.1073/pnas.88.16.6906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rutherford T. R., Clegg J. B., Weatherall D. J. K562 human leukaemic cells synthesise embryonic haemoglobin in response to haemin. Nature. 1979 Jul 12;280(5718):164–165. doi: 10.1038/280164a0. [DOI] [PubMed] [Google Scholar]
  28. Rutherford T. R., Weatherall D. J. Deficient heme synthesis as the cause of noninducibility of hemoglobin synthesis in a Friend erythroleukemia cell line. Cell. 1979 Feb;16(2):415–423. doi: 10.1016/0092-8674(79)90017-5. [DOI] [PubMed] [Google Scholar]
  29. Rutherford T., Clegg J. B., Higgs D. R., Jones R. W., Thompson J., Weatherall D. J. Embryonic erythroid differentiation in the human leukemic cell line K562. Proc Natl Acad Sci U S A. 1981 Jan;78(1):348–352. doi: 10.1073/pnas.78.1.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sarge K. D., Morimoto R. I. Surprising features of transcriptional regulation of heat shock genes. Gene Expr. 1991;1(3):169–173. [PMC free article] [PubMed] [Google Scholar]
  31. Sarge K. D., Zimarino V., Holm K., Wu C., Morimoto R. I. Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability. Genes Dev. 1991 Oct;5(10):1902–1911. doi: 10.1101/gad.5.10.1902. [DOI] [PubMed] [Google Scholar]
  32. Scharf K. D., Rose S., Zott W., Schöffl F., Nover L., Schöff F. Three tomato genes code for heat stress transcription factors with a region of remarkable homology to the DNA-binding domain of the yeast HSF. EMBO J. 1990 Dec;9(13):4495–4501. doi: 10.1002/j.1460-2075.1990.tb07900.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schuetz T. J., Gallo G. J., Sheldon L., Tempst P., Kingston R. E. Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in humans. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6911–6915. doi: 10.1073/pnas.88.16.6911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Singh M. K., Yu J. Accumulation of a heat shock-like protein during differentiation of human erythroid cell line K562. Nature. 1984 Jun 14;309(5969):631–633. doi: 10.1038/309631a0. [DOI] [PubMed] [Google Scholar]
  35. Sorger P. K. Heat shock factor and the heat shock response. Cell. 1991 May 3;65(3):363–366. doi: 10.1016/0092-8674(91)90452-5. [DOI] [PubMed] [Google Scholar]
  36. Stenzel K. H., Rubin A. L., Novogrodsky A. Mitogenic and co-mitogenic properties of hemin. J Immunol. 1981 Dec;127(6):2469–2473. [PubMed] [Google Scholar]
  37. Taylor I. C., Workman J. L., Schuetz T. J., Kingston R. E. Facilitated binding of GAL4 and heat shock factor to nucleosomal templates: differential function of DNA-binding domains. Genes Dev. 1991 Jul;5(7):1285–1298. doi: 10.1101/gad.5.7.1285. [DOI] [PubMed] [Google Scholar]
  38. Theodorakis N. G., Zand D. J., Kotzbauer P. T., Williams G. T., Morimoto R. I. Hemin-induced transcriptional activation of the HSP70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress response. Mol Cell Biol. 1989 Aug;9(8):3166–3173. doi: 10.1128/mcb.9.8.3166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Williams G. T., Morimoto R. I. Maximal stress-induced transcription from the human HSP70 promoter requires interactions with the basal promoter elements independent of rotational alignment. Mol Cell Biol. 1990 Jun;10(6):3125–3136. doi: 10.1128/mcb.10.6.3125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wu B. J., Kingston R. E., Morimoto R. I. Human HSP70 promoter contains at least two distinct regulatory domains. Proc Natl Acad Sci U S A. 1986 Feb;83(3):629–633. doi: 10.1073/pnas.83.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wu B., Hunt C., Morimoto R. Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol. 1985 Feb;5(2):330–341. doi: 10.1128/mcb.5.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Xiao H., Lis J. T. Germline transformation used to define key features of heat-shock response elements. Science. 1988 Mar 4;239(4844):1139–1142. doi: 10.1126/science.3125608. [DOI] [PubMed] [Google Scholar]