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  Identification and characterization of BATF3 as a context-specific coactivator of the glucocorticoid receptor

Birth, P., Schöne, S., Stelzl, U., & Meijsing, S. H. (2017). Identification and characterization of BATF3 as a context-specific coactivator of the glucocorticoid receptor. PLoS One, 12(7): e0181219. doi:10.1371/journal.pone.0181219.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-7756-A Version Permalink: http://hdl.handle.net/21.11116/0000-0000-7757-9
Genre: Journal Article

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Birth.pdf (Publisher version), 11MB
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© 2017 Birth et al.

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Birth, P.1, Author              
Schöne, S.2, Author              
Stelzl, Ulrich3, Author
Meijsing, S. H.2, Author              
Affiliations:
1Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433554              
2Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1479641              
3Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz and BioTechMed-Graz, Universitätsplatz 1, Graz, Austria, escidoc:persistent22              

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 Abstract: The ability of the glucocorticoid receptor (GR) to regulate the transcriptional output of genes relies on its interactions with transcriptional coregulators. However, which coregulators are required for GR-dependent activation is context-dependent and can be influenced by the sequence of the DNA bound by GR and by the nature of the GR isoform responsible for the regulation of a gene. Here, we screened for GR-interacting proteins for which the interaction signal differed between two GR isoforms GRalpha and GRgamma. These isoforms diverge by a single amino acid insertion in a domain, the lever arm, which adopts DNA sequence-specific conformations. We identify Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3), an AP-1 family transcription factor, as a GR coregulator whose interaction with GR is modulated by the lever arm. Further, a combination of experiments uncovered that BATF3 acts as a gene-specific coactivator of GR whose coactivator potency is influenced by the sequence of the GR binding site. Together, our findings suggest that GR isoform and the sequence of GR binding site influence the interaction of GR with BATF3, which might direct the assembly of gene-specific regulatory complexes to fine-tune the expression of individual GR target genes.

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Language(s): eng - English
 Dates: 2017-07-142017
 Publication Status: Published in print
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 Identifiers: DOI: 10.1371/journal.pone.0181219
ISSN: 1932-6203 (Electronic)
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Title: PLoS One
Source Genre: Journal
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Pages: - Volume / Issue: 12 (7) Sequence Number: e0181219 Start / End Page: - Identifier: -