Advertisement
Journal Article| Volume 266, ISSUE 15, P9805-9813, May 25, 1991

Sp1 and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes

Open AccessPublished:May 25, 1991DOI:https://doi.org/10.1016/S0021-9258(18)92891-7
      This paper is only available as a PDF. To read, Please Download here.
      Activation of hGH-1 expression is mediated by the pituitary-specific transcription factor GHF-I/Pit-I which binds the 5‘-flanking DNA at two sites: I (-96/-70) and II (-134/-106). Although the factor(s) which direct the placental-specific expression of hCS-1 are not known, hCS-1 sequences are transcriptionally active in pituitary cells. In the present study we examined the effects of sequence differences between hGH-1 and hCS-1 5‘-flanking DNAs in determining their basal and thyroid hormone-regulated promoter activities. We showed that Sp1 is a major determinant of both hGH-1 and hCS-1 promoter activities and that in hGH-1, binding and activation by Sp1 are modulated by interference from GHF-I/Pit-1 binding at the adjacent site II sequence. A single base which differed in site II of hCS-1 greatly reduced GHF-1/Pit-1 binding and thus facilitated binding and activation by Sp1. Further differences in promoter activity of hGH-1 and hCS-1 sequences were accounted for by a thyroid hormone-responsive element between -62/-48 in the hCS-1 gene. However, induction by T3 was independent of either Sp1 or GH-1/Pit-1 binding in the site II region. These data demonstrate that a small number of base changes between hGH and hCS promoter sequences subserve a number of mechanisms which may differentially modulate the expression of hGH and hCS genes.

      REFERENCES

        • Barsh G.S.
        • Seeburg P.H.
        • Gelinas R.E.
        Nucleic Acids Res. 1983; 11: 3939-3958
        • Hirt H.
        • Kimelman J.
        • Birnbaum M.J.
        • Chen E.Y.
        • Seeburg P.H.
        • Eberhardt N.L.
        • Barta A.
        DNA (NY). 1987; 6: 59-70
        • Lefevre C.
        • Imagawa M.
        • Dana S.
        • Grindlay J.
        • Bodner M.
        • Karin M.
        EMBO J. 1987; 6: 971-981
        • Nelson C.
        • Albert V.R.
        • Elsholtz H.P.
        • Lu L.I.-W.
        • Rosenfeld M.G.
        Science. 1988; 239: 1400-1405
        • Bodner M.
        • Karin M.
        Cell. 1987; 50: 267-275
        • Ingraham H.A.
        • Chen R.
        • Mangalam H.J.
        • Elsholtz H.P.
        • Flynn S.E.
        • Lin C.R.
        • Simmons D.M.
        • Swanson L.
        • Rosenfeld M.G.
        Cell. 1988; 55: 519-529
        • Castrillo J.-L.
        • Bodner M.
        • Karin M.
        Science. 1989; 243: 814-817
        • Theill L.E.
        • Castrillo J.-L.
        • Wu D.
        • Karin M.
        Nature. 1989; 342: 945-948
        • McCormick A.
        • Wu D.
        • Castrillo J.
        • Dana S.
        • Strobl J.
        • Thomp son E.B.
        • Karin M.
        Cell. 1988; 55: 379-389
        • Nickel B.E.
        • Kardami E.
        • Cattini P.
        Biochem. J. 1990; 267: 653-658
        • Lemaigre F.P.
        • Peers B.
        • Lafontaine D.A.
        • Mathy-Hartert M.
        • Rousseau G.G.
        • Belayew A.
        • Martial J.A.
        UNA (NY). 1989; 8: 149-159
        • Cattini P.A.
        • Eberhardt N.L.
        Nucleic Acids Res. 1987; 15: 1297-1309
        • Nachtigal M.W.
        • Nickel B.E.
        • Klassen M.E.
        • Zhang W.
        • Eberhardt N.L.
        • Cattini P.A.
        Nucleic Acids Res. 1989; 17: 4237-4337
        • Lemaigre F.P.
        • Courtois S.J.
        • Lafontaine D.A.
        • Rousseau G.G.
        Eur. J. Biochem. 1989; 181: 555-561
        • Courtois S.J.
        • Lafontaine D.A.
        • Lemaigre F.P.
        • Durviaux S.M.
        • Rousseau G.G.
        Nucleic Acids Res. 1990; 18: 57-64
        • Flug F.
        • Copp R.P.
        • Casanova J.
        • Horowitz Z.D.
        • Janocko L.
        • Plotnick M.
        • Samuels H.H.
        J. Biol. Chem. 1987; 262: 6373-6382
        • Glass C.K.
        • Franco R.
        • Weinberger C.
        • Albert V.R.
        • Evnas R.M.
        • Rosenfeld M.G.
        Nature. 1987; 329: 738-741
        • Koenig R.J.
        • Brent G.A.
        • Warne R.L.
        • Larsen P.R.
        • Moore D.D.
        Proc. Natl. Acad. Sei. U. S. A. 1987; 84: 5670-5674
        • Brent G.A.
        • Harney J.W.
        • Moore D.D.
        • Larsen P.R.
        Mol. Endocrinol. 1988; 2: 792-798
        • Lavin T.N.
        • Baxter J.D.
        • Horita S.
        J. Biol. Chem. 1988; 263: 9418-9426
        • Norman M.F.
        • Lavin T.N.
        • Baxter J.D.
        • West B.L.
        J. Biol. Chem. 1989; 264: 12063-12073
        • Eberhardt N.L.
        • Brooks R.L.
        • Leidig F.
        • Zhang W.G.
        • Lavin T.N.
        • Cattini P.A.
        Sizonenko P.C. Aubert M.L. in Developmental Endocrinology. Raven Press, New York1990: 221-237
        • Cattini P.A.
        • Anderson T.R.
        • Baxter J.D.
        • Mellon P.
        • Eberhardt N.L.
        J. Biol. Chem. 1986; 261: 13367-13372
        • Samuels H.H.
        • Stanley F.
        • Casanova J.
        Endocrinol ogy. 1979; 105: 80-85
        • Gorman C.M.
        • Moffat L.F.
        • Howard B.H.
        Mol. Cell. Biol. 1982; 2: 1044-1051
        • Schule R.
        • Muller M.
        • Otsuka-Murakami H.
        • Renkawitz R.
        Nature. 1988; 332: 87-90
        • Sambrook J.
        • Fritsch E.F.
        • Maniatis T.
        Molecular Cloning: A Laboratory Manual. Second Ed, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York1989
        • Kunkel T.A.
        Proc. Natl. Acad. Sei. U. S. A. 1985; 82: 488-492
        • Lee K.W.
        • Bindereif A.
        • Green M.R.
        Gene Anal. Tech. 1988; 5: 22-31
        • Catanzaro D.F.
        • West B.L.
        • Baxter J.D.
        • Reudelhuber T.L.
        Mol. Endocrinol. 1987; 1: 90-96
        • Apriletti J.W.
        • Baxter J.D.
        • Lavin T.N.
        J. Biol. Chem. 1988; 263: 9409-9417
        • Sturm R.
        • Baumruker T.
        • Franza Jr., B.R.
        • Herr W.
        Genes & Dev. 1987; 1: 1147-1160
        • Sleigh M.J.
        Anal. Biochem. 1986; 156: 251-256
        • Nielson D.A.
        • Chou J.
        • MacKrell A.J.
        • Casadaban M.J.
        • Steiner D.F.
        Proc. Natl. Acad. Sci. U. S. A. 1983; 80: 5198-5202
        • Brent G.A.
        • Harney J.W.
        • Warne R.L.
        • Moore D.D.
        • Larsen P.R.
        Mol. Endocrinol. 1989; 3: 1996-2004
        • Lemaigre F.P.
        • Lafontaine D.A.
        • Coutois S.J.
        • Durviaux S.M.
        • Rousseau G.G.
        Mol. Cell. Biol. 1990; 10: 1811-1814
        • Koenig R.J.
        • Lazar M.A.
        • Hodin R.A.
        • Brent G.A.
        • Larsen P.R.
        • Chin W.W.
        • Moore D.D.
        Nature. 1989; 337: 659-661
        • Watt F.
        • Molloy P.L.
        Nucleic Acids Res. 1988; 16: 1471-1485
        • Ingraham H.A.
        • Albert V.R.
        • Chen R.P.
        • Crenshaw III, E.B.
        • Elsholtz H.P.
        • He X.
        • Kapiloff M.S.
        • Mangalam H.J.
        • Swanson L.W.
        • Treacy M.N.
        • Rosenfeld M.G.
        Annu. Rev. Physiol. 1990; 52: 773-791
        • Kadonaga J.T.
        • Jones K.A.
        • Tjian R.
        Trends Biochem. Sci. 1986; 11: 20-23
        • Letovsky J.
        • Dynan W.S.
        Nucleic Acids Res. 1989; 7: 2639-2653
        • Dawson P.A.
        • Hoffman S.L.
        • van der Westhuyzen D.R.
        • Sudhof T.C.
        • Brown M.S.
        • Goldstein J.L.
        J. Biol. Chem. 1988; 263: 3372-3379
        • Stuart G.W.
        • Searle P.F.
        • Palmiter R.D.
        Nature 3 1. 1985; 7: 828-831
        • Westin G.
        • Schaffner W.
        EMBO J. 1988; 7: 3763-3770
        • Jansen L.
        • Bark C.
        • Petterson U.
        Nucleic Acids Res. 1987; 15: 4997-5016
        • Barlow J.W.
        • Voz M.L.J.
        • Eliard P.H.
        • Mathy-Hartert M.
        • DeNayer P.
        • Economidis I.V.
        • Belayew A.
        • Martial J.A.
        • Rousseau G.G.
        Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 9021-9025
        • Forman B.M.
        • Samuels H.H.
        Mol. Endocrinol. 1990; 4: 1293-1301
        • Schule R.
        • Muller M.
        • Kaltschmidt C.
        • Renkawitz R.
        Science. 1988; 242: 1418-1420
        • Buetti E.
        • Kuhnel B.
        J. Mol. Biol. 1986; 190: 379-389
        • Strahle U.
        • Schmid W.
        • Schötz G.
        EMBOJ. 1988; 7: 3389-3395
        • Murray M.B.
        • Towle H.C.
        Mol. Endocrinol. 1989; 3: 1434-1442
        • Burnside J.
        • Darling D.S.
        • Chin W.W.
        J. Biol Chem. 1990; 265: 2500-2504
        • West B.L.
        • Catanzaro D.F.
        • Mellon S.H.
        • Cattini P.A.
        • Baxter J.D.
        • Reudelhuber T.L.
        Mol. Cell. Biol. 1987; 7: 1193-1197
        • Chen E.Y.
        • Liao Y.C.
        • Smith D.H.
        • Barrerea-Saldana H.A.
        • Seeburg P.H.
        Genomics. 1989; 4: 479-497