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PMID: 8816448 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation.

Molecular and cellular biology ·Vol. 16 ·No. 10 ·1996-10-00 ·Pages 5365-74

Fischer DF, Gibbs S, van De Putte P, Backendorf C

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.

MeSH Terms
Base Sequence Calcium/pharmacology Cell Differentiation Cells, Cultured Chloramphenicol O-Acetyltransferase/biosynthesis Cornified Envelope Proline-Rich Proteins DNA Mutational Analysis DNA-Binding Proteins/metabolism Gene Expression Regulation Humans Keratinocytes/cytology,metabolism Kinetics Membrane Proteins/biosynthesis Oligodeoxyribonucleotides Promoter Regions, Genetic Protein Precursors/biosynthesis Recombinant Fusion Proteins/biosynthesis Skin/cytology TATA Box Transcription Factors/metabolism Transcription, Genetic Transfection Zinc Fingers
Chemicals
Cornified Envelope Proline-Rich Proteins DNA-Binding Proteins Membrane Proteins Oligodeoxyribonucleotides Protein Precursors Recombinant Fusion Proteins SPRR2A protein, human Transcription Factors Chloramphenicol O-Acetyltransferase Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fischer D F
Laboratory of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, The Netherlands.
Gibbs S
van De Putte P
Backendorf C
References (66)
66 references, click to expand
  1. Altered distribution of keratinization markers in epidermolytic hyperkeratosis.
    Arch Dermatol Res. 1995;287(8):705-11 PMID: 8554380
  2. The Ets family of proteins: weak modulators of gene expression in quest for transcriptional partners.
    Crit Rev Oncog. 1994;5(6):615-38 PMID: 8519813
  3. 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 May;90(5):739-43 PMID: 2452214
  4. Isolation, characterization, and UV-stimulated expression of two families of genes encoding polypeptides of related structure in human epidermal keratinocytes.
    Mol Cell Biol. 1988 May;8(5):2195-203 PMID: 3133554
  5. Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast.
    Curr Opin Cell Biol. 1995 Dec;7(6):798-805 PMID: 8608010
  6. 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 Feb 23;271(8):4561-8 PMID: 8626812
  7. 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 Aug;85(16):5839-43 PMID: 2842750
  8. Fibronectin inhibits the terminal differentiation of human keratinocytes.
    Nature. 1989 Jul 27;340(6231):307-9 PMID: 2473404
  9. 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 Aug 25;58(4):729-39 PMID: 2475256
  10. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
    Nucleic Acids Res. 1989 Aug 11;17(15):6419 PMID: 2771659
  11. Construction and properties of an Epstein-Barr-virus-derived cDNA expression vector for human cells.
    Gene. 1989 Dec 14;84(2):407-17 PMID: 2482230
  12. 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 Aug 11;18(15):4401-7 PMID: 2388825
  13. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
    Cell. 1990 Oct 19;63(2):303-12 PMID: 2208287
  14. Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes alpha 5 beta 1 integrin loss from the cell surface.
    Cell. 1990 Oct 19;63(2):425-35 PMID: 2145076
  15. Developmental expression of Sp1 in the mouse.
    Mol Cell Biol. 1991 Apr;11(4):2189-99 PMID: 2005904
  16. Cornifin, a cross-linked envelope precursor in keratinocytes that is down-regulated by retinoids.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11026-30 PMID: 1438308
  17. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system.
    Adv Immunol. 1992;52:263-81 PMID: 1442307
  18. Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes.
    Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 PMID: 1454515
  19. Effect of aging and habitual sun exposure on the genetic response of cultured human keratinocytes to solar-simulated irradiation.
    J Invest Dermatol. 1992 Dec;99(6):743-8 PMID: 1469287
  20. The Ets family of transcription factors.
    Eur J Biochem. 1993 Jan 15;211(1-2):7-18 PMID: 8425553
  21. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.
    Science. 1993 Feb 12;259(5097):971-4 PMID: 8438157
  22. Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11.
    Nucleic Acids Res. 1993 Jan 11;21(1):127-34 PMID: 8441607
  23. Skn-1a and Skn-1i: two functionally distinct Oct-2-related factors expressed in epidermis.
    Science. 1993 Apr 2;260(5104):78-82 PMID: 7682011
  24. A common origin for cornified envelope proteins?
    Nat Genet. 1992 Oct;2(2):91 PMID: 1303269
  25. Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins.
    Genomics. 1993 Jun;16(3):630-7 PMID: 8325635
  26. Expression of cornifin in squamous differentiating epithelial tissues, including psoriatic and retinoic acid-treated skin.
    J Invest Dermatol. 1993 Sep;101(3):268-74 PMID: 8370963
  27. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development.
    Cell. 1993 Oct 8;75(1):83-97 PMID: 8402903
  28. Expression patterns of loricrin in various species and tissues.
    Differentiation. 1993 Aug;54(1):25-34 PMID: 8405772
  29. Early events in signalling by interferons.
    Trends Biochem Sci. 1993 Sep;18(9):338-42 PMID: 7694399
  30. Regulation of proliferation-specific and differentiation-specific genes during senescence of human epidermal keratinocyte and mammary epithelial cells.
    Biochem Biophys Res Commun. 1993 Nov 30;197(1):46-54 PMID: 7902715
  31. Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21.
    Genomics. 1993 Oct;18(1):92-9 PMID: 8276421
  32. Control of growth regulatory and differentiation-specific genes in human epidermal keratinocytes by interferon gamma. Antagonism by retinoic acid and transforming growth factor beta 1.
    J Biol Chem. 1994 Jan 21;269(3):2016-22 PMID: 7904998
  33. Terminal differentiation of cultured human epidermal cells.
    Cell. 1977 Jun;11(2):405-16 PMID: 302145
  34. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells.
    Cell. 1975 Nov;6(3):331-43 PMID: 1052771
  35. Calcium regulation of growth and differentiation of mouse epidermal cells in culture.
    Cell. 1980 Jan;19(1):245-54 PMID: 6153576
  36. Corticoids and cultured human epidermal keratinocytes: specific intracellular binding and clinical efficacy.
    J Invest Dermatol. 1981 Mar;76(3):211-4 PMID: 6165779
  37. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  38. Calcium-induced reorganization of desmosomal components in cultured human keratinocytes.
    J Cell Biol. 1984 Dec;99(6):2211-5 PMID: 6209289
  39. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 PMID: 3881765
  40. Cloning and complete sequence of an HLA-A2 gene: analysis of two HLA-A alleles at the nucleotide level.
    J Immunol. 1985 Apr;134(4):2727-33 PMID: 2982951
  41. Effects of alpha and beta interferons on cultured human keratinocytes.
    J Invest Dermatol. 1985 Jul;85(1):70-4 PMID: 4008977
  42. An octamer oligonucleotide upstream of a TATA motif is sufficient for lymphoid-specific promoter activity.
    Nature. 1987 Sep 10-16;329(6135):174-8 PMID: 3627254
  43. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.
    Cell. 1987 Dec 24;51(6):1079-90 PMID: 3319186
  44. Low Ca2+ stripping of differentiating cell layers in human epidermal cultures: an in vitro model of epidermal regeneration.
    Exp Cell Res. 1988 Mar;175(1):63-73 PMID: 3345803
  45. Novel protein in human epidermal keratinocytes: regulation of expression during differentiation.
    Mol Cell Biol. 1988 May;8(5):2204-10 PMID: 3133555
  46. Heavy metal ions in transcription factors from HeLa cells: Sp1, but not octamer transcription factor requires zinc for DNA binding and for activator function.
    Nucleic Acids Res. 1988 Jul 11;16(13):5771-81 PMID: 3135532
  47. Evidence that cadherins play a role in the downregulation of integrin expression that occurs during keratinocyte terminal differentiation.
    J Cell Biol. 1994 Feb;124(4):589-600 PMID: 8106556
  48. Functional down-regulation of alpha 5 beta 1 integrin in keratinocytes is reversible but commitment to terminal differentiation is not.
    J Cell Sci. 1993 Dec;106 ( Pt 4):1131-8 PMID: 7510300
  49. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1.
    Cell. 1994 Jun 17;77(6):829-39 PMID: 8004672
  50. Sp1-mediated transcriptional activation is repressed by Sp3.
    EMBO J. 1994 Aug 15;13(16):3843-51 PMID: 8070411
  51. Direct evidence for homologous sequences on the paracentric regions of human chromosome 1.
    Genomics. 1994 May 15;21(2):359-63 PMID: 8088830
  52. Functional importance of an Sp1- and an NFkB-related nuclear protein in a keratinocyte-specific promoter of rabbit K3 keratin gene.
    J Biol Chem. 1994 Nov 11;269(45):28450-9 PMID: 7525574
  53. The pancornulins: a group of small proline rich-related cornified envelope precursors with bifunctional capabilities in isopeptide bond formation.
    J Invest Dermatol. 1995 Feb;104(2):204-10 PMID: 7829876
  54. The epidermis: rising to the surface.
    Curr Opin Genet Dev. 1994 Oct;4(5):725-36 PMID: 7531523
  55. High affinity binding sites for the Wilms' tumour suppressor protein WT1.
    Nucleic Acids Res. 1995 Jan 25;23(2):277-84 PMID: 7862533
  56. Regulation of cell surface beta 1 integrin levels during keratinocyte terminal differentiation.
    J Cell Biol. 1995 Mar;128(6):1209-19 PMID: 7534766
  57. In vivo and in vitro SPRR1 gene expression in normal and malignant keratinocytes.
    Exp Cell Res. 1995 Apr;217(2):217-26 PMID: 7698221
  58. Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors.
    Prog Nucleic Acid Res Mol Biol. 1995;50:191-224 PMID: 7754034
  59. Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family.
    Genomics. 1995 Feb 10;25(3):638-43 PMID: 7759097
  60. The small proline-rich proteins constitute a multigene family of differentially regulated cornified cell envelope precursor proteins.
    J Invest Dermatol. 1995 Jun;104(6):902-9 PMID: 7769256
  61. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain.
    Genes Dev. 1995 Jul 15;9(14):1679-93 PMID: 7622033
  62. The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope.
    J Biol Chem. 1995 Jul 28;270(30):17702-11 PMID: 7543090
  63. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes.
    Nature. 1995 Aug 17;376(6541):596-9 PMID: 7637809
  64. Changes in expression of members of the fos and jun families and myc network during terminal differentiation of human keratinocytes.
    Oncogene. 1995 Oct 5;11(7):1403-7 PMID: 7478564
  65. The 5' noncoding region of the mouse involucrin gene: comparison with the human gene and genes encoding other cornified envelope precursors.
    Mamm Genome. 1995 Sep;6(9):680-2 PMID: 8535084
  66. Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc-1/skn-1a.
    J Virol. 1996 Jan;70(1):10-6 PMID: 8523512
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.10.5365
Published
1996-10-00
Pages
5365-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231535
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.16.10.5365 PMC Full Text View journal details
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