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. 1988 Jun 24;16(12):5459–5472. doi: 10.1093/nar/16.12.5459

Organisation of the entire rabbit progesterone receptor mRNA and of the promoter and 5' flanking region of the gene.

M Misrahi 1, H Loosfelt 1, M Atger 1, C Mériel 1, V Zerah 1, P Dessen 1, E Milgrom 1
PMCID: PMC336778  PMID: 3387238

Abstract

cDNA clones corresponding to the 3' and 5' non coding regions of the rabbit progesterone receptor (rPR) mRNA and genomic clones corresponding to the promoter and 5' flanking region of this gene were isolated and sequenced up to nucleotide -2761. The 3' non coding region is very long (3058-3553 nucleotides) and contains three different polyadenylation sites. Primer extension experiments and S1 mapping showed the existence of 2 transcription initiation sites 699 and 712 bp upstream from the initiator ATG. The promoter region contains two modified TATA boxes: TAGAAA at -17 and TAGA at -37bp. A CAACT sequence is present at position -100 and one consensus binding site for the transcription factor Sp1 is found at position -51. A 317 bp sequence was observed (positions -2590 to -2273) which belongs to the C family of the short interspersed repeats of the rabbit. Sequences resembling the consensus for estrogen and progesterone responsive elements are observed at several locations in the 5' flanking region. The progesterone receptor is present in tissue extracts mainly as a mixture of two molecular species (110 and 79 kDa) whose origin remains currently debated. By Northern blot analysis we have shown, using rabbit and human mRNAs, that these receptor species are not derived from separate mRNAs. Transcription-translation experiments also showed that, at least in vitro, they are not derived by use of different translation initiation sites on the same messenger RNA.

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Selected References

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

  1. Arriza J. L., Weinberger C., Cerelli G., Glaser T. M., Handelin B. L., Housman D. E., Evans R. M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268–275. doi: 10.1126/science.3037703. [DOI] [PubMed] [Google Scholar]
  2. Azorin F., Rich A. Isolation of Z-DNA binding proteins from SV40 minichromosomes: evidence for binding to the viral control region. Cell. 1985 Jun;41(2):365–374. doi: 10.1016/s0092-8674(85)80009-x. [DOI] [PubMed] [Google Scholar]
  3. Bailly A., Le Page C., Rauch M., Milgrom E. Sequence-specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation. EMBO J. 1986 Dec 1;5(12):3235–3241. doi: 10.1002/j.1460-2075.1986.tb04634.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baniahmad A., Muller M., Steiner C., Renkawitz R. Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements. EMBO J. 1987 Aug;6(8):2297–2303. doi: 10.1002/j.1460-2075.1987.tb02504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birnbaumer M., Schrader W. T., O'Malley B. W. Assessment of structural similarities in chick oviduct progesterone receptor subunits by partial proteolysis of photoaffinity-labeled proteins. J Biol Chem. 1983 Jun 25;258(12):7331–7337. [PubMed] [Google Scholar]
  6. Cheng J. F., Printz R., Callaghan T., Shuey D., Hardison R. C. The rabbit C family of short, interspersed repeats. Nucleotide sequence determination and transcriptional analysis. J Mol Biol. 1984 Jun 15;176(1):1–20. doi: 10.1016/0022-2836(84)90379-6. [DOI] [PubMed] [Google Scholar]
  7. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  8. Giguère V., Yang N., Segui P., Evans R. M. Identification of a new class of steroid hormone receptors. Nature. 1988 Jan 7;331(6151):91–94. doi: 10.1038/331091a0. [DOI] [PubMed] [Google Scholar]
  9. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  10. Gronemeyer H., Turcotte B., Quirin-Stricker C., Bocquel M. T., Meyer M. E., Krozowski Z., Jeltsch J. M., Lerouge T., Garnier J. M., Chambon P. The chicken progesterone receptor: sequence, expression and functional analysis. EMBO J. 1987 Dec 20;6(13):3985–3994. doi: 10.1002/j.1460-2075.1987.tb02741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hollenberg S. M., Weinberger C., Ong E. S., Cerelli G., Oro A., Lebo R., Thompson E. B., Rosenfeld M. G., Evans R. M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature. 1985 Dec 19;318(6047):635–641. doi: 10.1038/318635a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horwitz K. B. The structure and function of progesterone receptors in breast cancer. J Steroid Biochem. 1987;27(1-3):447–457. doi: 10.1016/0022-4731(87)90339-6. [DOI] [PubMed] [Google Scholar]
  13. Huckaby C. S., Conneely O. M., Beattie W. G., Dobson A. D., Tsai M. J., O'Malley B. W. Structure of the chromosomal chicken progesterone receptor gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8380–8384. doi: 10.1073/pnas.84.23.8380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jantzen H. M., Strähle U., Gloss B., Stewart F., Schmid W., Boshart M., Miksicek R., Schütz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987 Apr 10;49(1):29–38. doi: 10.1016/0092-8674(87)90752-5. [DOI] [PubMed] [Google Scholar]
  15. Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
  16. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krust A., Green S., Argos P., Kumar V., Walter P., Bornert J. M., Chambon P. The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. EMBO J. 1986 May;5(5):891–897. doi: 10.1002/j.1460-2075.1986.tb04300.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Logeat F., Pamphile R., Loosfelt H., Jolivet A., Fournier A., Milgrom E. One-step immunoaffinity purification of active progesterone receptor. Further evidence in favor of the existence of a single steroid binding subunit. Biochemistry. 1985 Feb 12;24(4):1029–1035. doi: 10.1021/bi00325a034. [DOI] [PubMed] [Google Scholar]
  19. Loosfelt H., Atger M., Misrahi M., Guiochon-Mantel A., Meriel C., Logeat F., Benarous R., Milgrom E. Cloning and sequence analysis of rabbit progesterone-receptor complementary DNA. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9045–9049. doi: 10.1073/pnas.83.23.9045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Martinez E., Givel F., Wahli W. The estrogen-responsive element as an inducible enhancer: DNA sequence requirements and conversion to a glucocorticoid-responsive element. EMBO J. 1987 Dec 1;6(12):3719–3727. doi: 10.1002/j.1460-2075.1987.tb02706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McGuire W. L. Steroid hormone receptors in breast cancer treatment strategy. Recent Prog Horm Res. 1980;36:135–156. doi: 10.1016/b978-0-12-571136-4.50010-3. [DOI] [PubMed] [Google Scholar]
  22. Miesfeld R., Rusconi S., Godowski P. J., Maler B. A., Okret S., Wikström A. C., Gustafsson J. A., Yamamoto K. R. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell. 1986 Aug 1;46(3):389–399. doi: 10.1016/0092-8674(86)90659-8. [DOI] [PubMed] [Google Scholar]
  23. Misrahi M., Atger M., d'Auriol L., Loosfelt H., Meriel C., Fridlansky F., Guiochon-Mantel A., Galibert F., Milgrom E. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun. 1987 Mar 13;143(2):740–748. doi: 10.1016/0006-291x(87)91416-1. [DOI] [PubMed] [Google Scholar]
  24. Noda M., Furutani Y., Takahashi H., Toyosato M., Tanabe T., Shimizu S., Kikyotani S., Kayano T., Hirose T., Inayama S. Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. 1983 Oct 27-Nov 2Nature. 305(5937):818–823. doi: 10.1038/305818a0. [DOI] [PubMed] [Google Scholar]
  25. Okret S., Poellinger L., Dong Y., Gustafsson J. A. Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5899–5903. doi: 10.1073/pnas.83.16.5899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Owen D., Kühn L. C. Noncoding 3' sequences of the transferrin receptor gene are required for mRNA regulation by iron. EMBO J. 1987 May;6(5):1287–1293. doi: 10.1002/j.1460-2075.1987.tb02366.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Perrot-Applanat M., Groyer-Picard M. T., Lorenzo F., Jolivet A., Vu Hai M. T., Pallud C., Spyratos F., Milgrom E. Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors. Cancer Res. 1987 May 15;47(10):2652–2661. [PubMed] [Google Scholar]
  28. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  29. Rogers J. Molecular biology. CACA sequences - the ends and the means? Nature. 1983 Sep 8;305(5930):101–102. doi: 10.1038/305101a0. [DOI] [PubMed] [Google Scholar]
  30. Rousseau-Merck M. F., Misrahi M., Loosfelt H., Milgrom E., Berger R. Localization of the human progesterone receptor gene to chromosome 11q22-q23. Hum Genet. 1987 Nov;77(3):280–282. doi: 10.1007/BF00284486. [DOI] [PubMed] [Google Scholar]
  31. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  33. Seiler-Tuyns A., Walker P., Martinez E., Mérillat A. M., Givel F., Wahli W. Identification of estrogen-responsive DNA sequences by transient expression experiments in a human breast cancer cell line. Nucleic Acids Res. 1986 Nov 25;14(22):8755–8770. doi: 10.1093/nar/14.22.8755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  35. Strähle U., Klock G., Schütz G. A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7871–7875. doi: 10.1073/pnas.84.22.7871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Suske G., Wenz M., Cato A. C., Beato M. The uteroglobin gene region: hormonal regulation, repetitive elements and complete nucleotide sequence of the gene. Nucleic Acids Res. 1983 Apr 25;11(8):2257–2271. doi: 10.1093/nar/11.8.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Vu Hai M. T., Warembourg M., Milgrom E. Hormonal control of progesterone receptors. Ann N Y Acad Sci. 1977 Mar 11;286:199–209. doi: 10.1111/j.1749-6632.1977.tb29417.x. [DOI] [PubMed] [Google Scholar]
  38. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  39. Yaniv M. Regulation of eukaryotic gene expression by transactivating proteins and cis acting DNA elements. Biol Cell. 1984;50(3):203–216. doi: 10.1111/j.1768-322x.1984.tb00268.x. [DOI] [PubMed] [Google Scholar]
  40. de Thé H., Marchio A., Tiollais P., Dejean A. A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma. Nature. 1987 Dec 17;330(6149):667–670. doi: 10.1038/330667a0. [DOI] [PubMed] [Google Scholar]

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