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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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© 2015 by Cold Spring Harbor Laboratory Press
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http://www.ncbi.nlm.nih.gov/pubmed/25720775 (beliebiger Volltext)
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Starick, Stephan R.1, Autor           
Ibn-Salem, Jonas1, Autor
Jurk, Marcel1, Autor           
Hernandez, Céline2, Autor
Love, Michael I.3, Autor           
Chung, Ho-Ryun4, Autor           
Vingron, Martin5, Autor           
Thomas-Chollier, Morgane2, Autor
Meijsing, Sebastian H.1, Autor           
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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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2015-02-262015-06
 Publikationsstatus: Erschienen
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 Identifikatoren: DOI: 10.1101/gr.185157.114
ISSN: 1549-5469 (Electronic)1088-9051 (Print)
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Titel: Genome Res
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Cold Spring Harbor Laboratory Press
Seiten: - Band / Heft: 25 (6) Artikelnummer: - Start- / Endseite: 825 - 835 Identifikator: -