Archives of Dermatological Research

, Volume 305, Issue 5, pp 371–378 | Cite as

The POU domain transcription factors Oct-6 and Oct-11 negatively regulate loricrin gene expression in keratinocytes: association with AP-1 and Sp1/Sp3

  • Yasuhiro Kawachi
  • Yosuke Ishitsuka
  • Hiroshi Maruyama
  • Yasuhiro Fujisawa
  • Junichi Furuta
  • Yasuhiro Nakamura
  • Yoshiyuki Ishii
  • Eiko Ichikawa
  • Fujio Otsuka
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation and suppression of loricrin gene transcription in differentiated keratinocytes. Here, we identified a regulatory element in the proximal promoter region of the loricrin gene involved in suppression of its expression in keratinocytes. A database search indicated that this sequence contained a POU transcription factor binding motif. Electrophoretic mobility shift assay revealed that Oct-1, Oct-6, and Oct-11 actually bind to the motif. Constructs with point mutations in the POU-binding motif showed increased reporter activity, indicating that the POU factors negatively regulate loricrin gene transcription. Cotransfection experiments suggested that Oct-6 and Oct-11 suppress loricrin gene transcription in a cooperative manner with AP-1 and Sp1. Furthermore, in vitro experiments indicated that the Oct-6 and Oct-11 can physically associate with both AP-1 factors and Sp1/Sp3. These findings indicate that Oct-6 and Oct-11 contribute to the regulation of loricrin gene transcription via interaction with AP-1 factors and Sp1/Sp3.

Keywords

POU factors Oct-6 Oct-11 Loricrin Keratinocytes 
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References

  1. 1.
    Andersen B, Hariri A, Pittelkow MR et al (1997) Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression. J Biol Chem 272:15905–15913PubMedCrossRefGoogle Scholar
  2. 2.
    Andersen B, Rosenfeld MG (2001) POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev 22:2–35PubMedCrossRefGoogle Scholar
  3. 3.
    Andersen B, Schonemann MD, Flynn SE et al (1993) Skn-1a and Skn-1i: two functionally distinct Oct-2-related factors expressed in epidermis. Science 260:78–82PubMedCrossRefGoogle Scholar
  4. 4.
    Andersen B, Weinberg WC, Rennekampff O et al (1997) Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation. Gene Dev 11:1873–1884PubMedCrossRefGoogle Scholar
  5. 5.
    Beck IM, Muller M, Mentlein R et al (2007) Matrix metalloproteinase-19 expression in keratinocytes is repressed by transcription factors Tst-1 and Skn-1a: implications for keratinocyte differentiation. J Invest Dermatol 127:1107–1114PubMedCrossRefGoogle Scholar
  6. 6.
    Cabral A, Fischer DF, Vermeij WP et al (2003) Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation. J Biol Chem 278:17792–17799PubMedCrossRefGoogle Scholar
  7. 7.
    Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6:328–340PubMedCrossRefGoogle Scholar
  8. 8.
    Eckert RL, Crish JF, Banks EB et al (1997) The epidermis: genes on—genes off. J Invest Dermatol 109:501–509PubMedCrossRefGoogle Scholar
  9. 9.
    Enomoto K, Enomoto Y, Ishii Y et al (2003) Genes up- or down-regulated by expression of keratinocyte-specific POU transcription factor hSkn-1a. Biochem Biophys Res Commun 303:580–585PubMedCrossRefGoogle Scholar
  10. 10.
    Enomoto Y, Enomoto K, Kitamura T et al (2004) Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines. Oncogene 23:5014–5022PubMedCrossRefGoogle Scholar
  11. 11.
    Faus I, Hsu HJ, Fuchs E (1994) Oct-6: a regulator of keratinocyte gene expression in stratified squamous epithelia. Mol Cell Biol 14:3263–3275PubMedGoogle Scholar
  12. 12.
    Fischer DF, Gibbs S, van De Putte P et al (1996) Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation. Mol Cell Biol 16:5365–5374PubMedGoogle Scholar
  13. 13.
    Fisher C, Haydock PV, Dale BA (1987) Localization of profilaggrin mRNA in newborn rat skin by in situ hybridization. J Invest Dermatol 88:661–664PubMedCrossRefGoogle Scholar
  14. 14.
    Fuchs E, Green H (1980) Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell 19:1033–1042PubMedCrossRefGoogle Scholar
  15. 15.
    Harper JR, Greenhalgh DA, Yuspa SH (1988) Expression of transfected DNA by primary murine keratinocytes. J Invest Dermatol 91:150–153PubMedCrossRefGoogle Scholar
  16. 16.
    Hildesheim J, Foster RA, Chamberlin ME et al (1999) Characterization of the regulatory domains of the human skn-1a/Epoc-1/Oct-11 POU transcription factor. J Biol Chem 274:26399–26406PubMedCrossRefGoogle Scholar
  17. 17.
    Hildesheim J, Kuhn U, Yee CL et al (2001) The hSkn-1a POU transcription factor enhances epidermal stratification by promoting keratinocyte proliferation. J Cell Sci 114(Pt 10):1913–1923PubMedGoogle Scholar
  18. 18.
    Jang SI, Karaman-Jurukovska N, Morasso MI et al (2000) Complex interactions between epidermal POU domain and activator protein 1 transcription factors regulate the expression of the profilaggrin gene in normal human epidermal keratinocytes. J Biol Chem 275:15295–15304PubMedCrossRefGoogle Scholar
  19. 19.
    Jang SI, Steinert PM (2002) Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families. J Biol Chem 277:42268–42279PubMedCrossRefGoogle Scholar
  20. 20.
    Karlseder J, Rotheneder H, Wintersberger E (1996) Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol Cell Biol 16:1659–1667PubMedGoogle Scholar
  21. 21.
    Lena AM, Cipollone R, Amelio I et al (2010) Skn-1a/Oct-11 and DeltaNp63alpha exert antagonizing effects on human keratin expression. Biochem Biophys Res Commun 401:568–573PubMedCrossRefGoogle Scholar
  22. 22.
    Nagarajan P, Romano RA, Sinha S (2008) Transcriptional control of the differentiation program of interfollicular epidermal keratinocytes. Crit Rev Eukar Gene 18:57–79CrossRefGoogle Scholar
  23. 23.
    Nakamura Y, Kawachi Y, Xu X et al (2007) The combination of ubiquitous transcription factors AP-1 and Sp1 directs keratinocyte-specific and differentiation-specific gene expression in vitro. Exp Dermatol 16:143–150PubMedCrossRefGoogle Scholar
  24. 24.
    Pascal E, Tjian R (1991) Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism. Gene Dev 5:1646–1656PubMedCrossRefGoogle Scholar
  25. 25.
    Regnier M, Vaigot P, Darmon M et al (1986) Onset of epidermal differentiation in rapidly proliferating basal keratinocytes. J Invest Dermatol 87:472–476PubMedCrossRefGoogle Scholar
  26. 26.
    Rice RH, Green H (1979) Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell 18(3):681–694PubMedCrossRefGoogle Scholar
  27. 27.
    Roop D (1995) Defects in the barrier. Science 267:474–475PubMedCrossRefGoogle Scholar
  28. 28.
    Roop DR, Hawley-Nelson P, Cheng CK et al (1983) Keratin gene expression in mouse epidermis and cultured epidermal cells. Proc Natl Acad Sci USA 80:716–720PubMedCrossRefGoogle Scholar
  29. 29.
    Rothnagel JA, Greenhalgh DA, Gagne TA et al (1993) Identification of a calcium-inducible, epidermal-specific regulatory element in the 3′-flanking region of the human keratin 1 gene. J Invest Dermatol 101:506–513PubMedCrossRefGoogle Scholar
  30. 30.
    Rothnagel JA, Mehrel T, Idler WW et al (1987) The gene for mouse epidermal filaggrin precursor. Its partial characterization, expression, and sequence of a repeating filaggrin unit. J Biol Chem 262:15643–15648PubMedGoogle Scholar
  31. 31.
    Ryan AK, Rosenfeld MG (1997) POU domain family values: flexibility, partnerships, and developmental codes. Gene Dev 11:1207–1225PubMedCrossRefGoogle Scholar
  32. 32.
    Steven AC, Steinert PM (1994) Protein composition of cornified cell envelopes of epidermal keratinocytes. J Cell Sci 107(Pt 2):693–700PubMedGoogle Scholar
  33. 33.
    Sugihara TM, Kudryavtseva EI, Kumar V et al (2001) The POU domain factor Skin-1a represses the keratin 14 promoter independent of DNA binding. A possible role for interactions between Skn-1a and CREB-binding protein/p300. J Biol Chem 276:33036–33044PubMedCrossRefGoogle Scholar
  34. 34.
    Takemoto H, Tamai K, Akasaka E et al (2010) Relation between the expression levels of the POU transcription factors Skn-1a and Skn-1n and keratinocyte differentiation. J Dermatol Sci 60:203–205PubMedCrossRefGoogle Scholar
  35. 35.
    Welter JF, Gali H, Crish JF et al (1996) Regulation of human involucrin promoter activity by POU domain proteins. J Biol Chem 271:14727–14733PubMedCrossRefGoogle Scholar
  36. 36.
    Woodcock-Mitchell J, Eichner R, Nelson WG et al (1982) Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol 95(2 Pt 1):580–588PubMedCrossRefGoogle Scholar
  37. 37.
    Yamada K, Printz RL, Osawa H et al (1999) Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y. Biochem Biophys Res Commun 261:614–621PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Yasuhiro Kawachi
    • 1
  • Yosuke Ishitsuka
    • 1
  • Hiroshi Maruyama
    • 1
  • Yasuhiro Fujisawa
    • 1
  • Junichi Furuta
    • 1
  • Yasuhiro Nakamura
    • 1
  • Yoshiyuki Ishii
    • 1
  • Eiko Ichikawa
    • 1
  • Fujio Otsuka
    • 1
  1. 1.Department of Dermatology, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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