Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity
Schoene S, Jurk M, Helabad MB, Dror I, Lebars I, Kieffer B, Imhof P, Rohs R, Vingron M, Thomas-Chollier M, Meijsing SH (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 7
Article Number: 12621
DOI: 10.1038/ncomms12621
Abstract
The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes.
Authors with CRIS profile
Involved external institutions
Freie Universität Berlin
Germany (DE)
Université de Strasbourg (UDS)
France (FR)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics
Germany (DE)
University of Southern California (USC)
United States (USA) (US)
Germany (DE)
Université de Strasbourg (UDS)
France (FR)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics
Germany (DE)
University of Southern California (USC)
United States (USA) (US)
How to cite
APA:
Schoene, S., Jurk, M., Helabad, M.B., Dror, I., Lebars, I., Kieffer, B.,... Meijsing, S.H. (2016). Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity. Nature Communications, 7. https://doi.org/10.1038/ncomms12621
MLA:
Schoene, Stefanie, et al. "Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity." Nature Communications 7 (2016).
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