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  Identification and characterization of DNA sequences that prevent glucocorticoid receptor binding to nearby response elements

Telorac, J., Prykhozhij, S., Schöne, S., Meierhofer, D., Sauer, S., Thomas-Chollier, M., et al. (2016). Identification and characterization of DNA sequences that prevent glucocorticoid receptor binding to nearby response elements. Nucleic Acids Research (London), 44(13), 6142-6156. doi:10.1093/nar/gkw203.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-1364-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-1365-4
Genre: Journal Article

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© 2016 Oxford University Press

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 Creators:
Telorac, Jonas1, Author              
Prykhozhij, Sergey1, 2, Author              
Schöne, Stefanie1, Author              
Meierhofer, David3, Author              
Sauer, Sascha4, Author
Thomas-Chollier, Morgane 5, Author
Meijsing, Sebastiaan H.1, Author              
Affiliations:
1Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479641              
2Dalhousie University, Halifax, NS B3K 6R8, Canada , ou_persistent22              
3Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
4CU Systems Medicine, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany , ou_persistent22              
5Computational Systems Biology, Institut de Biologie de l'Ecole Normale, Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, F-75005 Paris, France , ou_persistent22              

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 Abstract: Out of the myriad of potential DNA binding sites of the glucocorticoid receptor (GR) found in the human genome, only a cell-type specific minority is actually bound, indicating that the presence of a recognition sequence alone is insufficient to specify where GR binds. Cooperative interactions with other transcription factors (TFs) are known to contribute to binding specificity. Here, we reasoned that sequence signals preventing GR recruitment to certain loci provide an alternative means to confer specificity. Motif analyses uncovered candidateNegative Regulatory Sequences(NRSs) that interfere with genomic GR binding. Subsequent functional analyses demonstrated that NRSs indeed prevent GR binding to nearby response elements. We show that NRS activity is conserved across species, found in most tissues and that they also interfere with the genomic binding of other TFs. Interestingly, the effects of NRSs appear not to be a simple consequence of changes in chromatin accessibility. Instead, we find that NRSs interact with proteins found at sub-nuclear structures called paraspeckles and that these proteins might mediate the repressive effects of NRSs. Together, our studies suggest that the joint influence of positive and negative sequence signals partition the genome into regions where GR can bind and those where it cannot.

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Language(s): eng - English
 Dates: 2016-03-252016-07-27
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: PII: gkw203
DOI: 10.1093/nar/gkw203
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Title: Nucleic Acids Research (London)
  Other : Nucleic Acids Res
Source Genre: Journal
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Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 44 (13) Sequence Number: - Start / End Page: 6142 - 6156 Identifier: ISSN: 0305-1048
CoNE: /journals/resource/110992357379342