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  ChIP-exo signal associated with DNA-binding motifs provides insight into the genomic binding of the glucocorticoid receptor and cooperating transcription factors

Starick, S. R., Ibn-Salem, J., Jurk, M., Hernandez, C., Love, M. I., Chung, H.-R., et al. (2015). ChIP-exo signal associated with DNA-binding motifs provides insight into the genomic binding of the glucocorticoid receptor and cooperating transcription factors. Genome Res, 25(6), 825-835. doi:10.1101/gr.185157.114.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-35A9-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-35AA-7
Genre: Journal Article

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© 2015 by Cold Spring Harbor Laboratory Press
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 Creators:
Starick, Stephan R.1, Author              
Ibn-Salem, Jonas1, Author
Jurk, Marcel1, Author              
Hernandez, Céline2, Author
Love, Michael I.3, Author              
Chung, Ho-Ryun4, Author              
Vingron, Martin5, Author              
Thomas-Chollier, Morgane2, Author
Meijsing, Sebastian 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              
2Institut de Biologie de l'Ecole Normale Supérieure, Institut National de la Santé et de la Recherche Médicale, U1024, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France , ou_persistent22              
3IMPRS 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              
4Computational Epigenetics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479658              
5Gene 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 classical DNA recognition sequence of the glucocorticoid receptor (GR) appears to be present at only a fraction of bound genomic regions. To identify sequences responsible for recruitment of this transcription factor (TF) to individual loci, we turned to the high-resolution ChIP-exo approach. We exploited this signal by determining footprint profiles of TF binding at single-base-pair resolution using ExoProfiler, a computational pipeline based on DNA binding motifs. When applied to our GR and the few available public ChIP-exo data sets, we find that ChIP-exo footprints are protein- and recognition sequence-specific signatures of genomic TF association. Furthermore, we show that ChIP-exo captures information about TFs other than the one directly targeted by the antibody in the ChIP procedure. Consequently, the shape of the ChIP-exo footprint can be used to discriminate between direct and indirect (tethering to other DNA-bound proteins) DNA association of GR. Together, our findings indicate that the absence of classical recognition sequences can be explained by direct GR binding to a broader spectrum of sequences than previously known, either as a homodimer or as a heterodimer binding together with a member of the ETS or TEAD families of TFs, or alternatively by indirect recruitment via FOX or STAT proteins. ChIP-exo footprints also bring structural insights and locate DNA:protein cross-link points that are compatible with crystal structures of the studied TFs. Overall, our generically applicable footprint-based approach uncovers new structural and functional insights into the diverse ways of genomic cooperation and association of TFs.

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Language(s): eng - English
 Dates: 2015-02-262015-06
 Publication Status: Published in print
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 Identifiers: DOI: 10.1101/gr.185157.114
ISSN: 1549-5469 (Electronic)1088-9051 (Print)
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Title: Genome Res
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 25 (6) Sequence Number: - Start / End Page: 825 - 835 Identifier: -