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  • Original Paper
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The human involucrin gene contains spatially distinct regulatory elements that regulate expression during early versus late epidermal differentiation

Oncogene volume 21, pages 738–747 (2002)Cite this article

A Corrigendum to this article was published on 24 May 2002

Abstract

Human involucrin (hINV) is a keratinocyte protein that is expressed in the suprabasal compartment of the epidermis and other stratifying surface epithelia. Involucrin gene expression is initiated early in the differentiation process and is maintained until terminal cell death. The distal regulatory region (DRR) is a segment of the hINV promoter (nucleotides −2473/−1953) that accurately recapitulates the normal pattern of suprabasal (spinous and granular layer) expression in transgenic mouse epithelia. To identify sequences that mediate expression at specific stages of differentiation, we divided the DRR into two segments, a 376 nucleotide upstream region (DRR−2473/−2100) and a 147 nucleotide downstream region (DRR−2100/−1953), and evaluated the ability of these sequences to drive expression in transgenic mice. The DRR−2473/−2100 segment drives expression at a level comparable to that observed for the DRR, but expression is restricted to the upper granular layers (i.e., no spinous layer expression). In contrast, the DRR−2100/−1953 segment does not drive expression. However, reassembling the DRR restores the complete range of expression. These results suggest that two distinct, spatially-separate elements are required to specify the complete differentiation-dependent program of involucrin gene expression. To identify specific transcription factor binding sites involved in this regulation, we mutated an activator protein-1 binding site, AP1-5, located within DRR−2473/-2100 segment. This site binds AP1 transcription factors present in mouse epidermal extracts, and its mutation eliminates appropriate hINV expression. This result suggests that AP1 factors participate as components of a multi-component transcription factor complex that is required for regulation.

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References

  • Banks-Schlegel S, Green H . 1981 J. Cell Biol. 90: 732–737

  • Banks EB, Crish JF, Eckert RL . 1999 Biochem. J. 337: 507–512

  • Banks EB, Crish JF, Welter JF, Eckert RL . 1998 Biochem. J. 331: 61–68

  • Bernerd F, Magnaldo T, Freedberg IM, Blumenberg M . 1993 Gene Expr. 3: 187–199

  • Bickenbach JR, Greer JM, Bundman DS, Rothnagel JA, Roop DR . 1995 J. Invest. Dermatol. 104: 405–410

  • Briata P, D'Anna F, Franzi AT, Gherzi R . 1993 Exp. Cell Res. 204: 136–146

  • Carroll JM, Albers KM, Garlick JA, Harrington R, Taichman LB . 1993 Proc. Natl. Acad. Sci. USA 90: 10270–10274

  • Casatorres J, Navarro JM, Blessing M, Jorcano JL . 1994 J. Biol. Chem. 269: 20489–20496

  • Chiang CM, Ge H, Wang Z, Hoffman A, Roeder RG . 1993 EMBO J. 12: 2749–2762

  • Cohen DR, Curran T . 1989 Crit. Rev. Oncog. 1: 65–88

  • Cohen DR, Ferreira PC, Gentz R, Franza Jr BR, Curran T . 1989 Genes Dev. 3: 173–184

  • Crish JF, Howard JM, Zaim TM, Murthy S, Eckert RL . 1993 Differentiation 53: 191–200

  • Crish JF, Zaim T, Eckert RL . 1998 J. Biol. Chem. 273: 30460–30465

  • DiSepio D, Jones A, Longley MA, Bundman D, Rothnagel JA, Roop DR . 1995a J. Biol. Chem. 270: 10792–10799

  • DiSepio D, Jones A, Longley MA, Bundman D, Rothnagel JA, Roop DR . 1995b J. Biol. Chem. 270: 10792–10799

  • Eckert RL, Crish JF, Banks EB, Welter JF . 1997b J. Invest. Dermatol. 109: 501–509

  • Eckert RL, Crish JF, Robinson NA . 1997a Physiol. Rev. 77: 397–424

  • Eckert RL, Green H . 1986 Cell 46: 583–589

  • Efimova T, Eckert RL . 2000 J. Biol. Chem. 275: 1601–1607

  • Efimova T, LaCelle P, Welter JF, Eckert RL . 1998 J. Biol. Chem. 273: 24387–24395

  • Fei Y, Matragoon S, Liou GI . 1995 Biotechniques 18: 984–987

  • Fisher C, Byers MR, Iadarola MJ, Powers EA . 1991 Development 111: 253–258

  • Green H . 1980 The Harvey Lectures 74: 101–139

  • Hohl D, Lichti U, Breitkreutz D, Steinert PM, Roop DR . 1991 J. Invest. Dermatol. 96: 414–418

  • Hohl D, Ruf Olano B, de Viragh PA, Huber M, Detrisac CJ, Schnyder UW, Roop DR . 1993 Differentiation 54: 25–34

  • Huff CA, Yuspa SH, Rosenthal DS, Rosenthal D . 1993 J. Biol. Chem. 268: 377–384

  • Kim SY, Chung SI, Steinert PM . 1995 J. Biol. Chem. 270: 18026–18035

  • LaCelle PT, Lambert A, Ekambaram MC, Robinson NA, Eckert RL . 1998 Skin Pharmacol. Appl. Skin Physiol. 11: 214–226

  • Lu B, Rothnagel JA, Longley MA, Tsai SY, Roop DR . 1994 J. Biol. Chem. 269: 7443–7449

  • Medvedev A, Saunders NA, Matsuura H, Chistokhina A, Jetten AM . 1999 J. Biol. Chem. 274: 3887–3896

  • Murphy GF, Flynn TC, Rice RH, Pinkus GS . 1984 J. Invest. Dermatol. 82: 453–457

  • Murthy S, Crish JF, Zaim TM, Eckert RL . 1993 J. Struct. Biol. 111: 68–76

  • Ng DC, Shafaee S, Lee D, Bikle DD . 2000 J. Biol. Chem. 275: 24080–24088

  • Nishina H, Sato H, Suzuki T, Sato M, Iba H . 1990 Proc. Natl. Acad. Sci. USA 87: 3619–3623

  • Rice RH, Green H . 1977 Cell 11: 417–422

  • Rice RH, Green H . 1979 Cell 18: 681–694

  • Rothnagel JA, Greenhalgh DA, Gagne TA, Longley MA, Roop DR . 1993 J. Invest. Dermatol. 101: 506–513

  • Rutberg SE, Saez E, Glick A, Dlugosz AA, Spiegelman BM, Yuspa SH . 1996 Oncogene 13: 167–176

  • Steinert PM . 1995 Cell Death Differ. 2: 33–40

  • Steinert PM, Marekov LN . 1997 J. Biol. Chem. 272: 2021–2030

  • Suzuki T, Okuno H, Yoshida T, Endo T, Nishina H, Iba H . 1991 Nucleic Acids Res. 19: 5537–5542

  • Takahashi H, Asano K, Manabe A, Kinouchi M, Ishida-Yamamoto A, Iizuka H . 1998 J. Invest. Dermatol. 110: 218–223

  • Takahashi H, Iizuka H . 1993 J. Invest. Dermatol. 100: 10–15

  • Thacher SM, Rice RH . 1985 Cell 40: 685–695

  • Welter JF, Crish JF, Agarwal C, Eckert RL . 1995 J. Biol. Chem. 270: 12614–12622

  • Welter JF, Eckert RL . 1995 Oncogene 11: 2681–2687

  • Welter JF, Gali H, Crish JF, Eckert RL . 1996 J. Biol. Chem. 271: 14727–14733

  • Xiao H, Hasegawa T, Isobe K . 2000 J. Biol. Chem. 275: 1371–1376

  • Xu L, Glass CK, Rosenfeld MG . 1999 Curr. Opin. Genet. Dev. 9: 140–147

  • Yamada K, Matsuki M, Morishima Y, Ueda E, Tabata K, Yasuno H, Suzuki M, Yamanishi K . 1997 Hum. Mol. Genet. 6: 2223–2231

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Acknowledgements

This work utilized the facilities of the Skin Diseases Research Center (AR39750) and was supported by grants from the National Institutes of Health (RL Eckert).

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, 44106-4970, Ohio, OH, USA

    James F Crish, Frederic Bone, Eric B Banks & Richard L Eckert

  2. Department of Dermatology, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, 44106-4970, Ohio, OH, USA

    Richard L Eckert

  3. Department of Reproductive Biology, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, 44106-4970, Ohio, OH, USA

    Richard L Eckert

  4. Department of Biochemistry, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, 44106-4970, Ohio, OH, USA

    Richard L Eckert

  5. Department of Oncology, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, 44106-4970, Ohio, OH, USA

    Richard L Eckert

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  1. James F Crish
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Correspondence to Richard L Eckert.

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Crish, J., Bone, F., Banks, E. et al. The human involucrin gene contains spatially distinct regulatory elements that regulate expression during early versus late epidermal differentiation. Oncogene 21, 738–747 (2002). https://doi.org/10.1038/sj.onc.1205038

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