Distal Sox Binding Elements of the αB-Crystallin Gene Show Lens Enhancer Activity in Transgenic Mouse Embryos

Nobuhiro Ijichi; Naomi Tsujimoto; Toru Iwaki; Yasuyuki Fukumaki; Akiko Iwaki

doi:10.1093/jb/mvh049

Nobuhiro Ijichi, Naomi Tsujimoto, Toru Iwaki, Yasuyuki Fukumaki, Akiko Iwaki

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Keywords: crystallin, enhancer, lens, transcription, transgenic-mouse

JOURNAL FREE ACCESS

2004 Volume 135 Issue 3 Pages 413-420

DOI https://doi.org/10.1093/jb/mvh049

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Published: March 01, 2004 Received: December 07, 2003 Available on J-STAGE: June 30, 2008 Accepted: January 22, 2004 Advance online publication: - Revised: -
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Date of correction: June 30, 2008 Reason for correction: - Correction: CITATION Details: Wrong : 1. Bloemendal, H., Hermsen, T., Dunia, I., and Benedetti, E. L. (1982) Association of crystallins with the plasma membrane. Exp. Eye Res. 35, 61-67
2. Bloemendal, H. and de Jong, W. W. (1991) Lens proteins and their genes. Prog. Nucleic Acid Res. Mol. Biol. 41, 259-281
3. Wistow, G. J. and Piatigorsky, J. (1988) Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Anna. Rev. Biochem. 57, 479-504
4. McAvoy, J. W. (1978) Cell division, cell elongation and the coordination of crystallin gene expression during lens morphogenesis in the rat. J. Embryol. Exp. Morphol. 45, 271-281
5. Robinson, M. L. and Overbeek, P. A. (1996) Differential expression of αA- and αB-crystallin during murine ocular development. Invest. Ophthalmol. Vis. Sci. 37, 2276-2284
6. Bhat, S. P. and Nagineni, C. N. (1989) αB subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochem. Biophys. Res. Commun. 158, 319-325
7. Dubin, R. A., Wawrousek, E. F., and Piatigorsky, J. (1989) Expression of the murine αB-crystallin gene is not restricted to the lens. Mot. Cell. Biol. 9, 1083-1091
8. Iwaki, T., Kume-Iwaki, A., and Goldman, J. E. (1990) Cellular distribution of αB-crystallin in non-lenticular tissues. J. Histochem. Cytochem. 38, 31-39
9. Iwaki, T., Kume-Iwaki, A., Liem, R. K., and Goldman, J. E. (1989) αB-Crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell 57, 71-78
10. Horwitz, J. (1992) α-Crystallin can function as a molecular chaperone. Proc. Natl. Acad. Sci. USA 89, 10449-10453
11. Clark, J. I. and Muchowski, P. J. (2000) Small heat-shock proteins and their potential role in human disease. Curr. Opin. Struct. Biol. 10, 52-59
12. Jackson, M., Gentleman, S., Lennox, G., Ward, L., Gray, T., Randall, K., Morrell, K., and Lowe, J. (1995) The cortical neuritic pathology of Huntington's disease. Neuropathol. Appl. Neurobiol. 21, 18-26
13. Kato, S., Hirano, A., Umahara, T., Llena, J. F., Herz, F., and Ohama, E. (1992) Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of αB-crystallin, ubiquitin and stressresponse protein 27. Acta Neuropathol. (Berl.) 84, 443-448
14. Lowe, J., Landon, M., Pike, I., Spendlove, I., McDermott, H., and Mayer, R. J. (1990) Dementia with beta-amyloid deposition: involvement of all-crystallin supports two main diseases. Lancet 336, 515-516
15. Dasgupta, S., Hohman, T. C., and Carper, D. (1992) Hypertonic stress induces αB-crystallin expression. Exp. Eye Res. 54, 461-470
16. Iwaki, T., Iwaki, A., Tateishi, J., Sakaki, Y., and Goldman, J. E. (1993) Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers. Am. J. Pathol. 143, 487-495
17. Kato, K., Goto, S., Hasegawa, K., and Inaguma, Y. (1993) Coinduction of two low-molecular-weight stress proteins, αB crystallin and HSP28, by heat or arsenite stress in human glioma cells. J. Biochem. 114, 640-647
18. Sadamitsu, C., Nagano, T., Fukumaki, Y., and Iwaki, A. (2001) Heat shock factor 2 is involved in the upregulation of αB-crystallin by high extracellular potassium. J. Biochem. 129, 813-820
19. Head, M. W., Hurwitz, L., and Goldman, J. E. (1996) Transcription regulation of αB-crystallin in astrocytes: analysis of HSF and AP1 activation by different types of physiological stress. J. Cell Sci. 109, 1029-1039
20. Gopal-Srivastava, R. and Piatigorsky, J. (1994) Identification of a lens-specific regulatory region (LSR) of the murine αB-crystallin gene. Nucleic Acids Res. 22, 1281-1286
21. Gopal-Srivastava, R., Cvekl, A., and Piatigorsky, J. (1996) Pax-6 and αB-crystallin/small heat shock protein gene regulation in the murine lens. Interaction with the lens-specific regions, LSR1 and LSR2. J Biol. Chem. 271, 23029-23036
22. Iwaki, A., Nagano, T., Nakagawa, M., Iwaki, T., and Fukumaki, Y. (1997) Identification and characterization of the gene encoding a new member of the a-crystallin/small hsp family, closely linked to the αB-crystallin gene in a head-to-head manner. Genomics 45, 386-394
23. Suzuki, A., Sugiyama, Y., Hayashi, Y., Nyu-i, N., Yoshida, M., Nonaka, I., Ishiura, S., Arahata, K., and Ohno, S. (1998) MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. J. Cell Biol. 140, 1113-1124
24. Higuchi, R., Krummel, B., and Saiki, R. K. (1988) A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 16, 7351-7367
25. Schreiber, E., Matthias, E, Muller, M. M., and Schaffner, W. (1989) Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Res. 17, 6419
26. Benjamin, I. J., Shelton, J., Garry, D. J., and Richardson, J. A. (1997) Temporospatial expression of the small HSP/αB-crystallin in cardiac and skeletal muscle during mouse development. Dev. Dyn. 208, 75-84
27. Haynes, J. I., II, Duncan, M. K., and Piatigorsky, J. (1996) Spatial and temporal activity of the αB-crystallin/small heat shock protein gene promoter in transgenic mice. Dev. Dyn. 207, 75-88
28. Kondoh, H. (1999) Transcription factors for lens development assessed in vivo. Curr. Opin. Genet. Dev. Dev. 9, 301-308
29. Ogino, H. and Yasuda, K. (2000) Sequential activation of transcription factors in lens induction. Dev. Growth Differ. 42, 437-448
30. Piatigorsky, J. (1998) Multifunctional lens crystallins and corneal enzymes. More than meets the eye. Ann. N. Y Acad. Sci. 842, 7-15
31. Kawauchi, S., Takahashi, S., Nakajima, O., Ogino, H., Morita, M., Nishizawa, M., Yasuda, K., and Yamamoto, M. (1999) Regulation of lens fiber cell differentiation by transcription factor c-Maf. J. Biol. Chem. 274, 19254-19260
32. Wingender, E., Chen, X., Hehl, R., Karas, H., Liebich, I., Matys, V., Meinhardt, T., Priio, M., Reuter, I., and Schacherer, F. (2000) TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res. 28, 316-319
33. Kataoka, K., Noda, M., and Nishizawa, M. (1994) Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol. Cell. Biol. 14, 700-712
34. Kamachi, Y., Uchikawa, M., Collignon, J., Lovell-Badge, R., and Kondoh, H. (1998) Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development 125, 2521-2532
35. Kamachi, Y., Uchikawa, M., and Kondoh, H. (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 16, 182-187
36. Wegner, M. (1999) From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res. 27, 1409-1420
37. Schepers, G. E., Teasdale, R. D., and Koopman, P. (2002) Twenty pairs of Sox: extent, homology, and nomenclature of the mouse and human Sox transcription factor gene families. Dev. Cell 3, 167-170
38. Wood, H. B. and Episkopou, V. (1999) Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech. Dev. 86, 197-201
39. Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P. N., and Lovell-Badge, R. (1996) A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Development 122, 509-520
40. Nishiguchi, S., Wood, H., Kondoh, H., Lovell-Badge, R., and Episkopou, V. (1998) Sox1 directly regulates the y-crystallin genes and is essential for lens development in mice. Genes Dev. 12, 776-781
41. Pevny, L. H., Sockanathan, S., Placzek, M., and Lovell-Badge, R. (1998) A role for SOX1 in neural determination. Development 125, 1967-1978
42. Gopal-Srivastava, R., Kays, W. T., and Piatigorsky, J. (2000) Enhancer-independent promoter activity of the mouse αB-crystallin/small heat shock protein gene in the lens and cornea of transgenic mice. Mech. Dev. 92, 125-134
43. Swamynathan, S. K. and Piatigorsky, J. (2002) Orientationdependent influence of an intergenic enhancer on the promoter activity of the divergently transcribed mouse Shsp/αB-crystallin and Mkbp/HspB2 genes. J. Biol. Chem. 277, 49700-49706
44. Ohtsuki, S., Levine, M., and Cai, H. N. (1998) Different core promoters possess distinct regulatory activities in the Drosophila embryo. Genes Dev. 12, 547-556
45. Calhoun, V. C., Stathopoulos, A., and Levine, M. (2002) Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila Antennapedia complex. Proc. Natl. Acad. Sci. USA 99, 9243-9247

Right : 1. Bloemendal, H., Hermsen, T., Dunia, I., and Benedetti, E. L. (1982) Association of crystallins with the plasma membrane. Exp. Eye Res. 35, 61-67
2. Bloemendal, H. and de Jong, W. W. (1991) Lens proteins and their genes. Prog. Nucleic Acid Res. Mol. Biol. 41, 259-281
3. Wistow, G. J. and Piatigorsky, J. (1988) Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Anna. Rev. Biochem. 57, 479-504
4. McAvoy, J. W. (1978) Cell division, cell elongation and the coordination of crystallin gene expression during lens morphogenesis in the rat. J. Embryol. Exp. Morphol. 45, 271-281
5. Robinson, M. L. and Overbeek, P. A. (1996) Differential expression of αA- and αB-crystallin during murine ocular development. Invest. Ophthalmol. Vis. Sci. 37, 2276-2284
6. Bhat, S. P. and Nagineni, C. N. (1989) αB subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochem. Biophys. Res. Commun. 158, 319-325
7. Dubin, R. A., Wawrousek, E. F., and Piatigorsky, J. (1989) Expression of the murine αB-crystallin gene is not restricted to the lens. Mot. Cell. Biol. 9, 1083-1091
8. Iwaki, T., Kume-Iwaki, A., and Goldman, J. E. (1990) Cellular distribution of αB-crystallin in non-lenticular tissues. J. Histochem. Cytochem. 38, 31-39
9. Iwaki, T., Kume-Iwaki, A., Liem, R. K., and Goldman, J. E. (1989) αB-Crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell 57, 71-78
10. Horwitz, J. (1992) α-Crystallin can function as a molecular chaperone. Proc. Natl. Acad. Sci. USA 89, 10449-10453
11. Clark, J. I. and Muchowski, P. J. (2000) Small heat-shock proteins and their potential role in human disease. Curr. Opin. Struct. Biol. 10, 52-59
12. Jackson, M., Gentleman, S., Lennox, G., Ward, L., Gray, T., Randall, K., Morrell, K., and Lowe, J. (1995) The cortical neuritic pathology of Huntington's disease. Neuropathol. Appl. Neurobiol. 21, 18-26
13. Kato, S., Hirano, A., Umahara, T., Llena, J. F., Herz, F., and Ohama, E. (1992) Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of αB-crystallin, ubiquitin and stressresponse protein 27. Acta Neuropathol. (Berl.) 84, 443-448
14. Lowe, J., Landon, M., Pike, I., Spendlove, I., McDermott, H., and Mayer, R. J. (1990) Dementia with beta-amyloid deposition: involvement of all-crystallin supports two main diseases. Lancet 336, 515-516
15. Dasgupta, S., Hohman, T. C., and Carper, D. (1992) Hypertonic stress induces αB-crystallin expression. Exp. Eye Res. 54, 461-470
16. Iwaki, T., Iwaki, A., Tateishi, J., Sakaki, Y., and Goldman, J. E. (1993) Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers. Am. J. Pathol. 143, 487-495
17. Kato, K., Goto, S., Hasegawa, K., and Inaguma, Y. (1993) Coinduction of two low-molecular-weight stress proteins, αB crystallin and HSP28, by heat or arsenite stress in human glioma cells. J. Biochem. 114, 640-647
18. Sadamitsu, C., Nagano, T., Fukumaki, Y., and Iwaki, A. (2001) Heat shock factor 2 is involved in the upregulation of αB-crystallin by high extracellular potassium. J. Biochem. 129, 813-820
19. Head, M. W., Hurwitz, L., and Goldman, J. E. (1996) Transcription regulation of αB-crystallin in astrocytes: analysis of HSF and AP1 activation by different types of physiological stress. J. Cell Sci. 109, 1029-1039
20. Gopal-Srivastava, R. and Piatigorsky, J. (1994) Identification of a lens-specific regulatory region (LSR) of the murine αB-crystallin gene. Nucleic Acids Res. 22, 1281-1286
21. Gopal-Srivastava, R., Cvekl, A., and Piatigorsky, J. (1996) Pax-6 and αB-crystallin/small heat shock protein gene regulation in the murine lens. Interaction with the lens-specific regions, LSR1 and LSR2. J Biol. Chem. 271, 23029-23036
22. Iwaki, A., Nagano, T., Nakagawa, M., Iwaki, T., and Fukumaki, Y. (1997) Identification and characterization of the gene encoding a new member of the a-crystallin/small hsp family, closely linked to the αB-crystallin gene in a head-to-head manner. Genomics 45, 386-394
23. Suzuki, A., Sugiyama, Y., Hayashi, Y., Nyu-i, N., Yoshida, M., Nonaka, I., Ishiura, S., Arahata, K., and Ohno, S. (1998) MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. J. Cell Biol. 140, 1113-1124
24. Higuchi, R., Krummel, B., and Saiki, R. K. (1988) A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 16, 7351-7367
25. Schreiber, E., Matthias, E, Muller, M. M., and Schaffner, W. (1989) Rapid detection of octamer binding proteins with ‘miniextracts’, prepared from a small number of cells. Nucleic Acids Res. 17, 6419
26. Benjamin, I. J., Shelton, J., Garry, D. J., and Richardson, J. A. (1997) Temporospatial expression of the small HSP/αB-crystallin in cardiac and skeletal muscle during mouse development. Dev. Dyn. 208, 75-84
27. Haynes, J. I., II, Duncan, M. K., and Piatigorsky, J. (1996) Spatial and temporal activity of the αB-crystallin/small heat shock protein gene promoter in transgenic mice. Dev. Dyn. 207, 75-88
28. Kondoh, H. (1999) Transcription factors for lens development assessed in vivo. Curr. Opin. Genet. Dev. Dev. 9, 301-308
29. Ogino, H. and Yasuda, K. (2000) Sequential activation of transcription factors in lens induction. Dev. Growth Differ. 42, 437-448
30. Piatigorsky, J. (1998) Multifunctional lens crystallins and corneal enzymes. More than meets the eye. Ann. N. Y Acad. Sci. 842, 7-15
31. Kawauchi, S., Takahashi, S., Nakajima, O., Ogino, H., Morita, M., Nishizawa, M., Yasuda, K., and Yamamoto, M. (1999) Regulation of lens fiber cell differentiation by transcription factor c-Maf. J. Biol. Chem. 274, 19254-19260
32. Wingender, E., Chen, X., Hehl, R., Karas, H., Liebich, I., Matys, V., Meinhardt, T., Priio, M., Reuter, I., and Schacherer, F. (2000) TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res. 28, 316-319
33. Kataoka, K., Noda, M., and Nishizawa, M. (1994) Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol. Cell. Biol. 14, 700-712
34. Kamachi, Y., Uchikawa, M., Collignon, J., Lovell-Badge, R., and Kondoh, H. (1998) Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development 125, 2521-2532
35. Kamachi, Y., Uchikawa, M., and Kondoh, H. (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 16, 182-187
36. Wegner, M. (1999) From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res. 27, 1409-1420
37. Schepers, G. E., Teasdale, R. D., and Koopman, P. (2002) Twenty pairs of Sox: extent, homology, and nomenclature of the mouse and human Sox transcription factor gene families. Dev. Cell 3, 167-170
38. Wood, H. B. and Episkopou, V. (1999) Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech. Dev. 86, 197-201
39. Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P. N., and Lovell-Badge, R. (1996) A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Development 122, 509-520
40. Nishiguchi, S., Wood, H., Kondoh, H., Lovell-Badge, R., and Episkopou, V. (1998) Sox1 directly regulates the y-crystallin genes and is essential for lens development in mice. Genes Dev. 12, 776-781
41. Pevny, L. H., Sockanathan, S., Placzek, M., and Lovell-Badge, R. (1998) A role for SOX1 in neural determination. Development 125, 1967-1978
42. Gopal-Srivastava, R., Kays, W. T., and Piatigorsky, J. (2000) Enhancer-independent promoter activity of the mouse αB-crystallin/small heat shock protein gene in the lens and cornea of transgenic mice. Mech. Dev. 92, 125-134
43. Swamynathan, S. K. and Piatigorsky, J. (2002) Orientationdependent influence of an intergenic enhancer on the promoter activity of the divergently transcribed mouse Shsp/αB-crystallin and Mkbp/HspB2 genes. J. Biol. Chem. 277, 49700-49706
44. Ohtsuki, S., Levine, M., and Cai, H. N. (1998) Different core promoters possess distinct regulatory activities in the Drosophila embryo. Genes Dev. 12, 547-556
45. Calhoun, V. C., Stathopoulos, A., and Levine, M. (2002) Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila Antennapedia complex. Proc. Natl. Acad. Sci. USA 99, 9243-9247

Date of correction: June 30, 2008 Reason for correction: - Correction: PDF FILE Details: -

Abstract

αB-Crystallin, a member of the small heat shock protein (sHSP) family, is expressed in various tissues including lens, heart, and skeletal muscle. Previously we identified the gene of HSPB2, another member of the sHSP family, located 1-kb upstream of the αB-crystallin gene in a head-to-head manner. In the present study, we found a highly conserved region of 220 by approximately 2.4-kb upstream of the all-crystallin gene and examined its role in expression of the αB-crystallin gene. Transgenic mice containing 3 kb of the upstream sequence of the αB-crystallin gene showed lacZ reporter gene expression in the lens as well as the myotome and heart on embryonic day 12.5. Deletion analysis revealed that the -2656/-2267 region including the conserved region with four putative Sox binding elements (E1-E4) exhibits lens enhancer activity toward the αB-crystallin promoter. Gel shift assays showed that the Sox1 and Sox2 proteins preferentially bound to E2 and E4. Moreover, disruption of E2 and E4 abolished the reporter gene expression in the lens. These results indicate that the newly identified enhancer with Sox elements activates the αB-crystallin promoter in the lens, although they are separated by the entire HSPB2 gene.

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