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PMID: 1570308 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Glucocorticoid receptor DNA-binding specificity is increased by the organization of DNA in nucleosomes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 9 ·1992-05-01 ·Pages 3884-8

Perlmann T

Abstract

A DNA fragment containing glucocorticoid receptor binding sites in the mouse mammary tumor virus promoter was reconstituted in vitro with histones to form nucleosome cores, which become positioned on the DNA fragment in a sequence-specific manner. Glucocorticoid receptor binding to specific DNA sequences was analyzed by quantitative DNase I footprinting. The receptor interacted with surprisingly high affinity with one of the binding sites in the reconstituted promoter, although it was reduced by a factor of approximately 2 compared with the same site in protein-free DNA. By contrast, the affinity for random genomic nucleosomal sites was drastically reduced compared with histone-free DNA. Thus, reconstituting the promoter in vitro resulted in a 60- to 70-fold increase in binding specificity. Such an increase in selective binding may help to explain the ability of glucocorticoid receptor to effectively locate its target sites in chromatin.

MeSH Terms
Animals Binding Sites Binding, Competitive Chromatin/metabolism DNA-Binding Proteins/metabolism In Vitro Techniques Nucleosomes/metabolism,ultrastructure Rats Receptors, Glucocorticoid/metabolism Regulatory Sequences, Nucleic Acid Structure-Activity Relationship Triamcinolone/metabolism
Chemicals
Chromatin DNA-Binding Proteins Nucleosomes Receptors, Glucocorticoid Triamcinolone
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Perlmann T
Department of Molecular Genetics, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
References (38)
38 references, click to expand
  1. Differential gene activation by glucocorticoids and progestins through the hormone regulatory element of mouse mammary tumor virus.
    Cell. 1988 May 6;53(3):371-82 PMID: 2835167
  2. The general affinity of lac repressor for E. coli DNA: implications for gene regulation in procaryotes and eucaryotes.
    Cell. 1975 Feb;4(2):107-11 PMID: 1092468
  3. Specific glucocorticoid receptor binding to DNA reconstituted in a nucleosome.
    EMBO J. 1988 Oct;7(10):3073-9 PMID: 2846275
  4. Nucleosome loss activates yeast downstream promoters in vivo.
    Cell. 1988 Dec 23;55(6):1137-45 PMID: 2849508
  5. Stoichiometric analysis of the specific interaction of the glucocorticoid receptor with DNA.
    J Biol Chem. 1986 Sep 5;261(25):11770-8 PMID: 3017946
  6. 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
  7. Nuclease hypersensitive regions with adjacent positioned nucleosomes mark the gene boundaries of the PHO5/PHO3 locus in yeast.
    EMBO J. 1986 Oct;5(10):2681-7 PMID: 3023055
  8. 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
  9. Statistical positioning of nucleosomes by specific protein-binding to an upstream activating sequence in yeast.
    J Mol Biol. 1988 Nov 5;204(1):109-27 PMID: 3063825
  10. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  11. Gene regulation by steroid hormones.
    Cell. 1989 Feb 10;56(3):335-44 PMID: 2644044
  12. Measurement of the binding of transcription factor Sp1 to a single GC box recognition sequence.
    Nucleic Acids Res. 1989 Apr 11;17(7):2639-53 PMID: 2717405
  13. Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1123-7 PMID: 2919163
  14. Protein/DNA architecture of the DNase I hypersensitive region of the Drosophila hsp26 promoter.
    EMBO J. 1988 Jul;7(7):2191-201 PMID: 2901349
  15. Tissue-specific DNaseI hypersensitive sites in the 5'-flanking sequences of the tryptophan oxygenase and the tyrosine aminotransferase genes.
    EMBO J. 1984 Sep;3(9):2015-20 PMID: 6149120
  16. Structure of the nucleosome core particle at 7 A resolution.
    Nature. 1984 Oct 11-17;311(5986):532-7 PMID: 6482966
  17. Binding of transcription factor TFIID to the major late promoter during in vitro nucleosome assembly potentiates subsequent initiation by RNA polymerase II.
    Cell. 1987 Nov 20;51(4):613-22 PMID: 3677170
  18. Tissue-specific in vitro transcription from the mouse albumin promoter.
    Cell. 1986 Dec 5;47(5):767-76 PMID: 3779841
  19. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA.
    Nature. 1991 Aug 8;352(6335):497-505 PMID: 1865905
  20. Inhibition of chromatin assembly in Xenopus oocytes correlates with derepression of the mouse mammary tumor virus promoter.
    Mol Cell Biol. 1991 Oct;11(10):5259-65 PMID: 1656227
  21. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors.
    Cell. 1991 Feb 8;64(3):565-72 PMID: 1846780
  22. Transcription factor access is mediated by accurately positioned nucleosomes on the mouse mammary tumor virus promoter.
    Mol Cell Biol. 1991 Feb;11(2):688-98 PMID: 1846670
  23. Quantitative analysis of the glucocorticoid receptor-DNA interaction at the mouse mammary tumor virus glucocorticoid response element.
    J Biol Chem. 1990 Oct 5;265(28):17222-9 PMID: 2170368
  24. A progesterone responsive element maps to the far upstream steroid dependent DNase hypersensitive site of chicken lysozyme chromatin.
    EMBO J. 1988 Jul;7(7):2063-73 PMID: 3416833
  25. DNA sequences outside the receptor-binding sites differently modulate the responsiveness of the mouse mammary tumour virus promoter to various steroid hormones.
    EMBO J. 1988 May;7(5):1403-10 PMID: 2842149
  26. Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones.
    Cell. 1987 Apr 24;49(2):203-10 PMID: 3568125
  27. A bacteriophage RNA polymerase transcribes in vitro through a nucleosome core without displacing it.
    Cell. 1987 Aug 28;50(5):801-8 PMID: 3621345
  28. Quantitative DNase footprint titration: a method for studying protein-DNA interactions.
    Methods Enzymol. 1986;130:132-81 PMID: 3773731
  29. Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoter.
    Cell. 1990 Mar 9;60(5):719-31 PMID: 2155706
  30. Lambda repressor: a model system for understanding protein-DNA interactions and protein stability.
    Adv Protein Chem. 1990;40:1-61 PMID: 2195849
  31. Nucleosome positioning can affect the function of a cis-acting DNA element in vivo.
    Nature. 1990 Jan 25;343(6256):387-9 PMID: 2405281
  32. A yeast protein that influences the chromatin structure of UASG and functions as a powerful auxiliary gene activator.
    Genes Dev. 1990 Apr;4(4):503-14 PMID: 2361590
  33. Protein-protein contacts in the glucocorticoid receptor homodimer influence its DNA binding properties.
    J Biol Chem. 1990 Feb 25;265(6):3535-42 PMID: 2303460
  34. Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element.
    Cell. 1984 Aug;38(1):29-38 PMID: 6088072
  35. Equilibrium studies of the cyclic AMP receptor protein-DNA interaction.
    J Mol Biol. 1984 Jan 25;172(3):241-62 PMID: 6319715
  36. 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
  37. Kinetic analysis of deoxyribonuclease I cleavages in the nucleosome core: evidence for a DNA superhelix.
    J Mol Biol. 1978 Sep 15;124(2):391-420 PMID: 568667
  38. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter.
    EMBO J. 1987 Aug;6(8):2321-8 PMID: 2822386
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.9.3884
Published
1992-05-01
Pages
3884-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC525595
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.9.3884 PMC Full Text View journal details
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