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  Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation

Love, M. I., Huska, M., Jurk, M., Schöpflin, R., Starick, S. R., Schwahn, K., et al. (2017). Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation. Nucleic Acids Research (London), 45(4), 1805-1819. doi:10.1093/nar/gkw1163.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-4750-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-4751-4
Genre: Journal Article

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 Creators:
Love, M. I.1, Author              
Huska, M.1, Author              
Jurk, M.2, Author              
Schöpflin, R.3, Author              
Starick, S. R.2, Author              
Schwahn, K., Author
Cooper, S. B., Author
Yamamoto, K. R., Author
Thomas-Chollier, M., Author
Vingron, M.4, Author              
Meijsing, S. H.2, Author              
Affiliations:
1IMPRS for Computational Biology and Scientific Computing - IMPRS-CBSC (Kirsten Kelleher), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479666              
2Mechanisms 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              
3Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
4Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter-proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined.

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Language(s): eng - English
 Dates: 2016-11-282017-02-28
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: PMID: 27903902
DOI: 10.1093/nar/gkw1163
ISSN: 1362-4962 (Electronic)0305-1048 (Print)
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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: 45 (4) Sequence Number: - Start / End Page: 1805 - 1819 Identifier: ISSN: 0305-1048
CoNE: /journals/resource/110992357379342