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Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity
Schoene, Stefanie ;  Jurk, Marcel ;  Helabad, Mahdi Bagherpoor ;  Dror, Iris ;  Lebars, Isabelle ;  Kieffer, Bruno ;  Imhof, Petra ;  Rohs, Remo ;  Vingron, Martin ;  Thomas-Chollier, Morgane ;  Meijsing, Sebastiaan H.

HaupttitelSequences flanking the core-binding site modulate glucocorticoid receptor structure and activity
AutorSchoene, Stefanie
AutorJurk, Marcel
AutorHelabad, Mahdi Bagherpoor
AutorDror, Iris
AutorLebars, Isabelle
AutorKieffer, Bruno
AutorImhof, Petra
AutorRohs, Remo
AutorVingron, Martin
AutorThomas-Chollier, Morgane
AutorMeijsing, Sebastiaan H.
Seitenzahl12 S.
Freie SchlagwörterDNA-binding proteins; Genome informatics; Solution-state NMR; Transcriptional regulatory elements
DDC570 Biowissenschaften; Biologie
Auch erschienen inNature Communications. - 7 (2016), Artikel Nr. 12621
ZusammenfassungThe 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.
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Fachbereich/EinrichtungFB Physik
Erscheinungsjahr2016
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am04.11.2016 - 10:19:55
Letzte Änderung04.11.2016 - 10:21:26
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000025674
DOI10.1038/ncomms12621
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