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PMID: 2586521 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription.

Molecular and cellular biology ·Vol. 9 ·No. 12 ·1989-12-00 ·Pages 5305-14

Drouin J, Trifiro MA, Plante RK, Nemer M, Eriksson P, Wrange O

Abstract

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.

MeSH Terms
Animals Base Sequence DNA/genetics,metabolism Genes Molecular Sequence Data Nucleotide Mapping Pituitary Gland, Anterior/metabolism Plasmids Pro-Opiomelanocortin/genetics Protein Binding Rats Receptors, Glucocorticoid/metabolism Restriction Mapping Suppression, Genetic Transcription, Genetic
Chemicals
Receptors, Glucocorticoid Pro-Opiomelanocortin DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Drouin J
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, Quebec, Canada.
Trifiro M A
Plante R K
Nemer M
Eriksson P
Wrange O
References (67)
67 references, click to expand
  1. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus.
    Nature. 1983 Aug 25-31;304(5928):749-52 PMID: 6310405
  2. Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein.
    Science. 1986 Feb 14;231(4739):699-704 PMID: 3080805
  3. Inhibition of restriction endonuclease Nci I cleavage by phosphorothioate groups and its application to oligonucleotide-directed mutagenesis.
    Nucleic Acids Res. 1986 Dec 22;14(24):9679-98 PMID: 3027659
  4. Hormonal response region in the mouse mammary tumor virus long terminal repeat can be dissociated from the proviral promoter and has enhancer properties.
    Proc Natl Acad Sci U S A. 1985 Feb;82(4):1020-4 PMID: 2983325
  5. 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):7871-5 PMID: 2891134
  6. The human beta-interferon gene enhancer is under negative control.
    Cell. 1986 May 23;45(4):601-10 PMID: 3708688
  7. Characterization of the purified activated glucocorticoid receptor from rat liver cytosol.
    J Biol Chem. 1984 Apr 10;259(7):4534-41 PMID: 6707018
  8. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters.
    Nature. 1985 Feb 21-27;313(6004):706-9 PMID: 2983219
  9. Tissue-specific regulation of pituitary proopiomelanocortin gene transcription by corticotropin-releasing hormone, 3',5'-cyclic adenosine monophosphate, and glucocorticoids.
    Mol Endocrinol. 1987 Oct;1(10):677-82 PMID: 2856398
  10. Selective effect of androgens on LH and FSH release in anterior pituitary cells in culture.
    Endocrinology. 1976 Jun;98(6):1528-34 PMID: 132345
  11. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5 PMID: 6438633
  12. Yeast HAP1 activator binds to two upstream activation sites of different sequence.
    Cell. 1987 Apr 10;49(1):19-27 PMID: 3030565
  13. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids.
    Nature. 1981 Nov 19;294(5838):228-32 PMID: 6272123
  14. Enhancer and promoter elements directing activation and glucocorticoid repression of the alpha 1-fetoprotein gene in hepatocytes.
    Mol Cell Biol. 1988 Apr;8(4):1398-407 PMID: 2454390
  15. Repression of transcription in yeast.
    Cell. 1985 Aug;42(1):3-4 PMID: 3893745
  16. Sequences in the promoter region of the chicken lysozyme gene required for steroid regulation and receptor binding.
    Cell. 1984 Jun;37(2):503-10 PMID: 6722881
  17. Structure of the rat pro-opiomelanocortin (POMC) gene.
    FEBS Lett. 1985 Nov 25;193(1):54-8 PMID: 2998878
  18. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus.
    Cell. 1981 Dec;27(2 Pt 1):245-55 PMID: 6277498
  19. Antagonist effect of RU 486 on transcription of glucocorticoid-regulated genes.
    Exp Cell Res. 1987 Dec;173(2):425-30 PMID: 3121370
  20. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus.
    Cell. 1986 Jul 18;46(2):283-90 PMID: 3013424
  21. Pituitary-specific expression and glucocorticoid regulation of a proopiomelanocortin fusion gene in transgenic mice.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8890-4 PMID: 3194396
  22. RU 38486: potent antiglucocorticoid activity correlated with strong binding to the cytosolic glucocorticoid receptor followed by an impaired activation.
    J Steroid Biochem. 1984 Jan;20(1):271-6 PMID: 6708512
  23. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement.
    Nature. 1987 Jan 22-28;325(6102):365-8 PMID: 3808033
  24. Gene regulation by steroid hormones.
    Cell. 1989 Feb 10;56(3):335-44 PMID: 2644044
  25. Hormonal regulation of the bovine prolactin promoter in rat pituitary tumor cells.
    J Biol Chem. 1985 Oct 5;260(22):12246-51 PMID: 2995368
  26. Distinct sequence elements involved in the glucocorticoid regulation of the mouse mammary tumor virus promoter identified by linker scanning mutagenesis.
    J Mol Biol. 1986 Aug 5;190(3):379-89 PMID: 3023641
  27. The effects of dexamethasone on in vitro collagen gene expression.
    J Biol Chem. 1987 May 25;262(15):6955-8 PMID: 3584102
  28. Hormonally mediated negative regulation of human pro-opiomelanocortin gene expression after transfection into mouse L cells.
    Mol Cell Biol. 1985 Sep;5(9):2443-53 PMID: 3016528
  29. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo.
    Cell. 1983 Jun;33(2):489-99 PMID: 6190571
  30. Products & materials.
    Science. 1988 Aug 19;241(4868):992 PMID: 17731452
  31. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
    Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 PMID: 6091052
  32. Stoichiometric analysis of the specific interaction of the glucocorticoid receptor with DNA.
    J Biol Chem. 1986 Sep 5;261(25):11770-8 PMID: 3017946
  33. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor.
    Nature. 1988 Mar 3;332(6159):87-90 PMID: 2831456
  34. Steroid receptor regulated transcription of specific genes and gene networks.
    Annu Rev Genet. 1985;19:209-52 PMID: 3909942
  35. In vivo protein-DNA interactions in a glucocorticoid response element require the presence of the hormone.
    Nature. 1986 Dec 18-31;324(6098):686-8 PMID: 2879246
  36. Selective reduction of proadrenocorticotropin/endorphin proteins and messenger ribonucleic acid activity in mouse pituitary tumor cells by glucocorticoids.
    Biochemistry. 1979 Oct 30;18(22):4907-15 PMID: 228704
  37. Most of the coding region of rat ACTH beta--LPH precursor gene lacks intervening sequences.
    Nature. 1980 Dec 11;288(5791):610-3 PMID: 6255341
  38. The regulation of transcription initiation in bacteria.
    Annu Rev Genet. 1985;19:355-87 PMID: 3936407
  39. An amino-terminal fragment of lac repressor binds specifically to lac operator.
    Proc Natl Acad Sci U S A. 1978 Dec;75(12):5851-4 PMID: 16592594
  40. Transcriptional inhibition by a glucocorticoid receptor-beta-galactosidase fusion protein.
    Cell. 1988 Dec 23;55(6):1109-14 PMID: 3144438
  41. Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain.
    Cell. 1988 Mar 11;52(5):685-95 PMID: 3345568
  42. Corticotropin releasing factor increases proopiomelanocortin messenger RNA in mouse anterior pituitary tumor cells.
    J Biol Chem. 1985 Dec 15;260(29):15477-81 PMID: 2999118
  43. Pro-opiomelanocortin gene: a model for negative regulation of transcription by glucocorticoids.
    J Cell Biochem. 1987 Dec;35(4):293-304 PMID: 3326882
  44. Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by dexamethasone.
    J Biol Chem. 1987 Dec 5;262(34):16300-4 PMID: 2824488
  45. Specific glucocorticoid receptor binding to DNA reconstituted in a nucleosome.
    EMBO J. 1988 Oct;7(10):3073-9 PMID: 2846275
  46. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region.
    Cell. 1983 Dec;35(2 Pt 1):381-92 PMID: 6317184
  47. Rapid suppression of alpha 1-fetoprotein gene transcription by dexamethasone in developing rat liver.
    Biochemistry. 1983 Aug 30;22(18):4296-302 PMID: 6194818
  48. Effects of steroid hormones on the level of corticotropin messenger RNA activity in cultured mouse-pituitary-tumor cells.
    Eur J Biochem. 1978 May;86(1):61-6 PMID: 207519
  49. Regulation of pro-opiomelanocortin gene transcription in individual cell nuclei.
    Science. 1986 Dec 5;234(4781):1265-9 PMID: 3775385
  50. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor.
    Cell. 1987 Apr 10;49(1):39-46 PMID: 3829127
  51. Opposite regulation of pro-opiomelanocortin gene transcription by glucocorticoids and CRH.
    Mol Cell Endocrinol. 1985 Apr;40(1):25-32 PMID: 3873366
  52. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity.
    Nucleic Acids Res. 1978 Sep;5(9):3157-70 PMID: 212715
  53. Contacts between hormone receptor and DNA double helix within a glucocorticoid regulatory element of mouse mammary tumor virus.
    Proc Natl Acad Sci U S A. 1984 May;81(10):3029-33 PMID: 6328488
  54. Glucocorticoid inhibition of transcription from episomal proopiomelanocortin gene promoter.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):8903-7 PMID: 3024155
  55. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter.
    EMBO J. 1987 Aug;6(8):2321-8 PMID: 2822386
  56. Steroid-dependent interaction of transcription factors with the inducible promoter of mouse mammary tumor virus in vivo.
    Cell. 1987 Jan 30;48(2):261-70 PMID: 3026639
  57. The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function.
    Cell. 1988 Jul 15;54(2):199-207 PMID: 3390864
  58. A small region of the mouse mammary tumor virus long terminal repeat confers glucocorticoid hormone regulation on a linked heterologous gene.
    Proc Natl Acad Sci U S A. 1983 Oct;80(19):5866-70 PMID: 6310597
  59. Tissue-specific activity of the pro-opiomelanocortin gene promoter.
    Mol Cell Biol. 1987 Nov;7(11):4058-64 PMID: 3431549
  60. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements.
    Cell. 1988 Jul 29;54(3):313-23 PMID: 3396073
  61. Differential binding of the chicken ovalbumin upstream promoter (COUP) transcription factor to two different promoters.
    J Biol Chem. 1988 Sep 15;263(26):13470-4 PMID: 3047126
  62. Glucocorticoids regulate proopiomelanocortin gene expression in vivo at the levels of transcription and secretion.
    Proc Natl Acad Sci U S A. 1983 Nov;80(22):6982-6 PMID: 6316340
  63. Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene.
    Genes Dev. 1988 Sep;2(9):1144-54 PMID: 3192076
  64. Glucocorticoid regulation of pro-opiomelanocortin gene transcription in the rat pituitary.
    J Biol Chem. 1984 Feb 25;259(4):2166-70 PMID: 6546571
  65. 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):347-59 PMID: 3607873
  66. Functional domains of the human glucocorticoid receptor.
    Cell. 1986 Aug 29;46(5):645-52 PMID: 3742595
  67. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.9.12.5305-5314.1989
Published
1989-12-00
Pages
5305-14
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363695
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.9.12.5305-5314.1989 PMC Full Text View journal details
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