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. 1990 Jan 11;18(1):57–64. doi: 10.1093/nar/18.1.57

Nuclear factor-I and activator protein-2 bind in a mutually exclusive way to overlapping promoter sequences and trans-activate the human growth hormone gene.

S J Courtois 1, D A Lafontaine 1, F P Lemaigre 1, S M Durviaux 1, G G Rousseau 1
PMCID: PMC330203  PMID: 2308836

Abstract

Transcription of the human growth hormone (hGH) gene and its regulation are controlled by trans-acting factors that bind to hGH gene promoter sequences. Several DNase I footprints have been described within 500 bp of this promoter, one of which (-289 to -267) has not yet been ascribed to a defined factor. By DNase I footprinting, gel mobility shift, and methylation interference assays with extracts from HeLa cells and GH-producing pituitary tumor (GC) cells, we show that this factor belongs to the NF-I family. When NF-I was competed out of the cell extracts, the trans-acting factor AP-2 bound to the same site as NF-I. AP-2 was present not only in HeLa cells, but also in GC cells albeit at a much lower concentration. Consistent with the mutually exclusive binding of NF-I and AP-2, their methylation interference patterns included four guanine residues that were crucial for binding of both NF-I and AP-2. Cell-free transcription from the hGH gene promoter showed that these two factors can transactivate this gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barberis A., Superti-Furga G., Busslinger M. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell. 1987 Jul 31;50(3):347–359. doi: 10.1016/0092-8674(87)90489-2. [DOI] [PubMed] [Google Scholar]
  2. Bedo G., Santisteban P., Aranda A. Retinoic acid regulates growth hormone gene expression. Nature. 1989 May 18;339(6221):231–234. doi: 10.1038/339231a0. [DOI] [PubMed] [Google Scholar]
  3. Bodner M., Karin M. A pituitary-specific trans-acting factor can stimulate transcription from the growth hormone promoter in extracts of nonexpressing cells. Cell. 1987 Jul 17;50(2):267–275. doi: 10.1016/0092-8674(87)90222-4. [DOI] [PubMed] [Google Scholar]
  4. Brent G. A., Harney J. W., Moore D. D., Larsen P. R. Multihormonal regulation of the human, rat, and bovine growth hormone promoters: differential effects of 3',5'-cyclic adenosine monophosphate, thyroid hormone, and glucocorticoids. Mol Endocrinol. 1988 Sep;2(9):792–798. doi: 10.1210/mend-2-9-792. [DOI] [PubMed] [Google Scholar]
  5. Buetti E., Kühnel B., Diggelmann H. Dual function of a nuclear factor I binding site in MMTV transcription regulation. Nucleic Acids Res. 1989 Apr 25;17(8):3065–3078. doi: 10.1093/nar/17.8.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carthew R. W., Chodosh L. A., Sharp P. A. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985 Dec;43(2 Pt 1):439–448. doi: 10.1016/0092-8674(85)90174-6. [DOI] [PubMed] [Google Scholar]
  7. Castrillo J. L., Bodner M., Karin M. Purification of growth hormone-specific transcription factor GHF-1 containing homeobox. Science. 1989 Feb 10;243(4892):814–817. doi: 10.1126/science.2563596. [DOI] [PubMed] [Google Scholar]
  8. Chodosh L. A., Baldwin A. S., Carthew R. W., Sharp P. A. Human CCAAT-binding proteins have heterologous subunits. Cell. 1988 Apr 8;53(1):11–24. doi: 10.1016/0092-8674(88)90483-7. [DOI] [PubMed] [Google Scholar]
  9. Cordingley M. G., Riegel A. T., Hager G. L. Steroid-dependent interaction of transcription factors with the inducible promoter of mouse mammary tumor virus in vivo. Cell. 1987 Jan 30;48(2):261–270. doi: 10.1016/0092-8674(87)90429-6. [DOI] [PubMed] [Google Scholar]
  10. Dana S., Karin M. Induction of human growth hormone promoter activity by the adenosine 3',5'-monophosphate pathway involves a novel responsive element. Mol Endocrinol. 1989 May;3(5):815–821. doi: 10.1210/mend-3-5-815. [DOI] [PubMed] [Google Scholar]
  11. Eliard P. H., Marchand M. J., Rousseau G. G., Formstecher P., Mathy-Hartert M., Belayew A., Martial J. A. Binding of the human glucocorticoid receptor to defined regions in the human growth hormone and placental lactogen genes. DNA. 1985 Dec;4(6):409–417. doi: 10.1089/dna.1985.4.409. [DOI] [PubMed] [Google Scholar]
  12. Gil G., Smith J. R., Goldstein J. L., Slaughter C. A., Orth K., Brown M. S., Osborne T. F. Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8963–8967. doi: 10.1073/pnas.85.23.8963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hynes N., van Ooyen A. J., Kennedy N., Herrlich P., Ponta H., Groner B. Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3637–3641. doi: 10.1073/pnas.80.12.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Imagawa M., Chiu R., Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. doi: 10.1016/0092-8674(87)90152-8. [DOI] [PubMed] [Google Scholar]
  15. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  16. Lefevre C., Imagawa M., Dana S., Grindlay J., Bodner M., Karin M. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor. EMBO J. 1987 Apr;6(4):971–981. doi: 10.1002/j.1460-2075.1987.tb04847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lemaigre F. P., Courtois S. J., Lafontaine D. A., Rousseau G. G. Evidence that the upstream stimulatory factor and the Sp1 transcription factor bind in vitro to the promoter of the human-growth-hormone gene. Eur J Biochem. 1989 May 15;181(3):555–561. doi: 10.1111/j.1432-1033.1989.tb14760.x. [DOI] [PubMed] [Google Scholar]
  18. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  19. Mercurio F., Karin M. Transcription factors AP-3 and AP-2 interact with the SV40 enhancer in a mutually exclusive manner. EMBO J. 1989 May;8(5):1455–1460. doi: 10.1002/j.1460-2075.1989.tb03528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  21. Miller W. L., Eberhardt N. L. Structure and evolution of the growth hormone gene family. Endocr Rev. 1983 Spring;4(2):97–130. doi: 10.1210/edrv-4-2-97. [DOI] [PubMed] [Google Scholar]
  22. Moore D. D., Marks A. R., Buckley D. I., Kapler G., Payvar F., Goodman H. M. The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor. Proc Natl Acad Sci U S A. 1985 Feb;82(3):699–702. doi: 10.1073/pnas.82.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nowock J., Borgmeyer U., Püschel A. W., Rupp R. A., Sippel A. E. The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer. Nucleic Acids Res. 1985 Mar 25;13(6):2045–2061. doi: 10.1093/nar/13.6.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Paonessa G., Gounari F., Frank R., Cortese R. Purification of a NF1-like DNA-binding protein from rat liver and cloning of the corresponding cDNA. EMBO J. 1988 Oct;7(10):3115–3123. doi: 10.1002/j.1460-2075.1988.tb03178.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roesler W. J., Vandenbark G. R., Hanson R. W. Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem. 1988 Jul 5;263(19):9063–9066. [PubMed] [Google Scholar]
  26. Rosenfeld P. J., Kelly T. J. Purification of nuclear factor I by DNA recognition site affinity chromatography. J Biol Chem. 1986 Jan 25;261(3):1398–1408. [PubMed] [Google Scholar]
  27. Santoro C., Mermod N., Andrews P. C., Tjian R. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature. 1988 Jul 21;334(6179):218–224. doi: 10.1038/334218a0. [DOI] [PubMed] [Google Scholar]
  28. Schüle R., Muller M., Kaltschmidt C., Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science. 1988 Dec 9;242(4884):1418–1420. doi: 10.1126/science.3201230. [DOI] [PubMed] [Google Scholar]
  29. Strähle U., Schmid W., Schütz G. Synergistic action of the glucocorticoid receptor with transcription factors. EMBO J. 1988 Nov;7(11):3389–3395. doi: 10.1002/j.1460-2075.1988.tb03212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Williams T., Admon A., Lüscher B., Tjian R. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Genes Dev. 1988 Dec;2(12A):1557–1569. doi: 10.1101/gad.2.12a.1557. [DOI] [PubMed] [Google Scholar]
  31. de Vries E., van Driel W., van den Heuvel S. J., van der Vliet P. C. Contactpoint analysis of the HeLa nuclear factor I recognition site reveals symmetrical binding at one side of the DNA helix. EMBO J. 1987 Jan;6(1):161–168. doi: 10.1002/j.1460-2075.1987.tb04734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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