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Mol Cell Biol. Sep 1992; 12(9): 4230–4241.
PMCID: PMC360331

Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters.

Abstract

The Pax-8 gene, a member of the murine family of paired box-containing genes (Pax genes), is expressed in adult thyroid and in cultured thyroid cell lines. The Pax-8 protein binds, through its paired domain, to the promoters of thyroglobulin and thyroperoxidase, genes that are exclusively expressed in the thyroid. In both promoters, the binding site of Pax-8 overlaps with that of TTF-1, a homeodomain-containing protein involved in the activation of thyroid-specific transcription. Pax-8 activates transcription from cotransfected thyroperoxidase and thyroglobulin promoters, indicating that it may be involved in the establishment, control, or maintenance of the thyroid-differentiated phenotype. Thus, the promoters of thyroglobulin and thyroperoxidase represent the first identified natural targets for transcriptional activation by a paired domain-containing protein.

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  • Affolter M, Schier A, Gehring WJ. Homeodomain proteins and the regulation of gene expression. Curr Opin Cell Biol. 1990 Jun;2(3):485–495. [PubMed]
  • Ambesi-Impiombato FS, Coon HG. Thyroid cells in culture. Int Rev Cytol Suppl. 1979;(10):163–172. [PubMed]
  • Ambesi-Impiombato FS, Parks LA, Coon HG. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3455–3459. [PMC free article] [PubMed]
  • Andersson S, Davis DL, Dahlbäck H, Jörnvall H, Russell DW. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989 May 15;264(14):8222–8229. [PubMed]
  • Avvedimento VE, Musti AM, Ueffing M, Obici S, Gallo A, Sanchez M, DeBrasi D, Gottesman ME. Reversible inhibition of a thyroid-specific trans-acting factor by Ras. Genes Dev. 1991 Jan;5(1):22–28. [PubMed]
  • Balling R, Deutsch U, Gruss P. undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1. Cell. 1988 Nov 4;55(3):531–535. [PubMed]
  • Baumgartner S, Bopp D, Burri M, Noll M. Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis. Genes Dev. 1987 Dec;1(10):1247–1267. [PubMed]
  • Bopp D, Burri M, Baumgartner S, Frigerio G, Noll M. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell. 1986 Dec 26;47(6):1033–1040. [PubMed]
  • Bopp D, Jamet E, Baumgartner S, Burri M, Noll M. Isolation of two tissue-specific Drosophila paired box genes, Pox meso and Pox neuro. EMBO J. 1989 Nov;8(11):3447–3457. [PMC free article] [PubMed]
  • Burri M, Tromvoukis Y, Bopp D, Frigerio G, Noll M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 1989 Apr;8(4):1183–1190. [PMC free article] [PubMed]
  • Chalepakis G, Fritsch R, Fickenscher H, Deutsch U, Goulding M, Gruss P. The molecular basis of the undulated/Pax-1 mutation. Cell. 1991 Sep 6;66(5):873–884. [PubMed]
  • Church GM, Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. [PMC free article] [PubMed]
  • Civitareale D, Lonigro R, Sinclair AJ, Di Lauro R. A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. EMBO J. 1989 Sep;8(9):2537–2542. [PMC free article] [PubMed]
  • Damante G, Di Lauro R. Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5388–5392. [PMC free article] [PubMed]
  • Deutsch U, Dressler GR, Gruss P. Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development. Cell. 1988 May 20;53(4):617–625. [PubMed]
  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. [PMC free article] [PubMed]
  • Francis-Lang H, Price M, Polycarpou-Schwarz M, Di Lauro R. Cell-type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression. Mol Cell Biol. 1992 Feb;12(2):576–588. [PMC free article] [PubMed]
  • Frasch M, Levine M. Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila. Genes Dev. 1987 Nov;1(9):981–995. [PubMed]
  • Fried M, Crothers DM. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. [PMC free article] [PubMed]
  • Frigerio G, Burri M, Bopp D, Baumgartner S, Noll M. Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell. 1986 Dec 5;47(5):735–746. [PubMed]
  • Fusco A, Berlingieri MT, Di Fiore PP, Portella G, Grieco M, Vecchio G. One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes. Mol Cell Biol. 1987 Sep;7(9):3365–3370. [PMC free article] [PubMed]
  • Fusco A, Pinto A, Ambesi-Impiombato FS, Vecchio G, Tsuchida N. Transformation of rat thyroid epithelial cells by Kirsten murine sarcoma virus. Int J Cancer. 1981 Nov 15;28(5):655–662. [PubMed]
  • Fusco A, Pinto A, Tramontano D, Tajana G, Vecchio G, Tsuchida N. Block in the expression of differentiation markers of rat thyroid epithelial cells by transformation with Kirsten murine sarcoma virus. Cancer Res. 1982 Feb;42(2):618–626. [PubMed]
  • Gehring WJ, Müller M, Affolter M, Percival-Smith A, Billeter M, Qian YQ, Otting G, Wüthrich K. The structure of the homeodomain and its functional implications. Trends Genet. 1990 Oct;6(10):323–329. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Goulding MD, Chalepakis G, Deutsch U, Erselius JR, Gruss P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 1991 May;10(5):1135–1147. [PMC free article] [PubMed]
  • GRUNEBERG H. Genetical studies on the skeleton of the mouse. XXII. The development of Danforth's short-tail. J Embryol Exp Morphol. 1958 Mar;6(1):124–148. [PubMed]
  • Guazzi S, Price M, De Felice M, Damante G, Mattei MG, Di Lauro R. Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. EMBO J. 1990 Nov;9(11):3631–3639. [PMC free article] [PubMed]
  • Herbomel P, Bourachot B, Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. [PubMed]
  • Kessel M, Gruss P. Murine developmental control genes. Science. 1990 Jul 27;249(4967):374–379. [PubMed]
  • Kissinger CR, Liu BS, Martin-Blanco E, Kornberg TB, Pabo CO. Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell. 1990 Nov 2;63(3):579–590. [PubMed]
  • Kuwabara MD, Sigman DS. Footprinting DNA-protein complexes in situ following gel retardation assays using 1,10-phenanthroline-copper ion: Escherichia coli RNA polymerase-lac promoter complexes. Biochemistry. 1987 Nov 17;26(23):7234–7238. [PubMed]
  • Lazzaro D, Price M, de Felice M, Di Lauro R. The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development. 1991 Dec;113(4):1093–1104. [PubMed]
  • Morrissey D, Askew D, Raj L, Weir M. Functional dissection of the paired segmentation gene in Drosophila embryos. Genes Dev. 1991 Sep;5(9):1684–1696. [PubMed]
  • Musti AM, Ursini VM, Avvedimento EV, Zimarino V, Di Lauro R. A cell type specific factor recognizes the rat thyroglobulin promoter. Nucleic Acids Res. 1987 Oct 26;15(20):8149–8166. [PMC free article] [PubMed]
  • Plachov D, Chowdhury K, Walther C, Simon D, Guenet JL, Gruss P. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development. 1990 Oct;110(2):643–651. [PubMed]
  • Qian YQ, Billeter M, Otting G, Müller M, Gehring WJ, Wüthrich K. The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989 Nov 3;59(3):573–580. [PubMed]
  • Scott MP, Tamkun JW, Hartzell GW., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. [PubMed]
  • Sinclair AJ, Lonigro R, Civitareale D, Ghibelli L, Di Lauro R. The tissue-specific expression of the thyroglobulin gene requires interaction between thyroid-specific and ubiquitous factors. Eur J Biochem. 1990 Oct 24;193(2):311–318. [PubMed]
  • Smith DB, Johnson KS. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. [PubMed]
  • Treisman J, Harris E, Desplan C. The paired box encodes a second DNA-binding domain in the paired homeo domain protein. Genes Dev. 1991 Apr;5(4):594–604. [PubMed]
  • Walther C, Guenet JL, Simon D, Deutsch U, Jostes B, Goulding MD, Plachov D, Balling R, Gruss P. Pax: a murine multigene family of paired box-containing genes. Genomics. 1991 Oct;11(2):424–434. [PubMed]
  • Wolberger C, Vershon AK, Liu B, Johnson AD, Pabo CO. Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions. Cell. 1991 Nov 1;67(3):517–528. [PubMed]

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