Interdependent Transcription Control Elements Regulate the Expression of the SPRR2A Gene During Keratinocyte Terminal Differentiation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1996 Oct 1

PMID 8816448

Citations 21

Authors

D F Fischer

S Gibbs

P Van de Putte

C Backendorf

Affiliations

Soon will be listed here.

Abstract

Expression of the SPRR2A gene, a member of the small proline-rich family of cornified cell envelope precursor proteins, is strictly linked to keratinocyte terminal differentiation both in vivo and in vitro. In this study, we explored the molecular mechanisms underlying this regulation in transiently transfected primary keratinocytes induced to differentiate in vitro. Deletion mapping and site-directed mutagenesis of SPRR2A promoter-chloramphenicol acetyltransferase constructs indicate that four transcription control elements are essential and sufficient for promoter activity. These elements were further characterized by electrophoretic mobility shift and identified as (i) an inverted octamer doublet, bound by the POU domain factor Oct-11 (Skn-1a/i, Epoc-1), (ii) an interferon-stimulated response element recognized by interferon regulatory factors 1 and 2, (iii) an Ets binding site partially overlapping the interferon-stimulated response element, and (iv) a TG box recognized by the Sp1 family of zinc finger transcription factors. Destruction of a single terminal differentiation element is sufficient to completely abolish transcription from the SPRR2A promoter, indicating that these transcription control elements function in concert in an interdependent manner. Apparently, integration of signals transmitted by the above-mentioned transcription factors is necessary and sufficient to promote gene expression during keratinocyte terminal differentiation.

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References

Ishida-Yamamoto A, Iizuka H, Manabe M, Oguin W, Hohl D, Kartasova T . Altered distribution of keratinization markers in epidermolytic hyperkeratosis. Arch Dermatol Res. 1995; 287(8):705-11. DOI: 10.1007/BF01105793. View

Crepieux P, Coll J, Stehelin D . The Ets family of proteins: weak modulators of gene expression in quest for transcriptional partners. Crit Rev Oncog. 1994; 5(6):615-38. View

Read J, Watt F . A model for in vitro studies of epidermal homeostasis: proliferation and involucrin synthesis by cultured human keratinocytes during recovery after stripping off the suprabasal layers. J Invest Dermatol. 1988; 90(5):739-43. DOI: 10.1111/1523-1747.ep12560940. View

Kartasova T, Van de Putte P . Isolation, characterization, and UV-stimulated expression of two families of genes encoding polypeptides of related structure in human epidermal keratinocytes. Mol Cell Biol. 1988; 8(5):2195-203. PMC: 363401. DOI: 10.1128/mcb.8.5.2195-2203.1988. View

Waskiewicz A, Cooper J . Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin Cell Biol. 1995; 7(6):798-805. DOI: 10.1016/0955-0674(95)80063-8. View

Lee J, Jang S, Yang J, Markova N, Steinert P . The proximal promoter of the human transglutaminase 3 gene. Stratified squamous epithelial-specific expression in cultured cells is mediated by binding of Sp1 and ets transcription factors to a proximal promoter element. J Biol Chem. 1996; 271(8):4561-8. View

Martin M, Piette J, Yaniv M, Tang W, Folk W . Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins. Proc Natl Acad Sci U S A. 1988; 85(16):5839-43. PMC: 281860. DOI: 10.1073/pnas.85.16.5839. View

Adams J, Watt F . Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature. 1989; 340(6231):307-9. DOI: 10.1038/340307a0. View

Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A . Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989; 58(4):729-39. DOI: 10.1016/0092-8674(89)90107-4. View

10.

Schreiber E, Matthias P, Muller M, Schaffner W . Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989; 17(15):6419. PMC: 318318. DOI: 10.1093/nar/17.15.6419. View

11.

Belt P, Groeneveld H, Teubel W, Van de Putte P, Backendorf C . Construction and properties of an Epstein-Barr-virus-derived cDNA expression vector for human cells. Gene. 1989; 84(2):407-17. DOI: 10.1016/0378-1119(89)90515-5. View

12.

Gibbs S, Lohman F, Teubel W, Van de Putte P, Backendorf C . Characterization of the human spr2 promoter: induction after UV irradiation or TPA treatment and regulation during differentiation of cultured primary keratinocytes. Nucleic Acids Res. 1990; 18(15):4401-7. PMC: 331257. DOI: 10.1093/nar/18.15.4401. View

13.

Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, Taniguchi T . Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell. 1990; 63(2):303-12. DOI: 10.1016/0092-8674(90)90163-9. View

14.

Adams J, Watt F . Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes alpha 5 beta 1 integrin loss from the cell surface. Cell. 1990; 63(2):425-35. DOI: 10.1016/0092-8674(90)90175-e. View

15.

Saffer J, Jackson S, Annarella M . Developmental expression of Sp1 in the mouse. Mol Cell Biol. 1991; 11(4):2189-99. PMC: 359911. DOI: 10.1128/mcb.11.4.2189-2199.1991. View

16.

Marvin K, George M, Fujimoto W, Saunders N, Bernacki S, Jetten A . Cornifin, a cross-linked envelope precursor in keratinocytes that is down-regulated by retinoids. Proc Natl Acad Sci U S A. 1992; 89(22):11026-30. PMC: 50476. DOI: 10.1073/pnas.89.22.11026. View

17.

Tanaka N, Taniguchi T . Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. Adv Immunol. 1992; 52:263-81. DOI: 10.1016/s0065-2776(08)60877-9. View

18.

Hagen G, Muller S, Beato M, Suske G . Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes. Nucleic Acids Res. 1992; 20(21):5519-25. PMC: 334381. DOI: 10.1093/nar/20.21.5519. View

19.

Garmyn M, Yaar M, Boileau N, Backendorf C, Gilchrest B . Effect of aging and habitual sun exposure on the genetic response of cultured human keratinocytes to solar-simulated irradiation. J Invest Dermatol. 1992; 99(6):743-8. DOI: 10.1111/1523-1747.ep12614470. View

20.

Wasylyk B, Hahn S, Giovane A . The Ets family of transcription factors. Eur J Biochem. 1993; 211(1-2):7-18. DOI: 10.1007/978-3-642-78757-7_2. View