Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity - Archive ouverte HAL
Article Dans Une Revue Nature Communications Année : 2016

Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity

Résumé

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.
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Dates et versions

hal-03352071 , version 1 (22-09-2021)

Identifiants

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Stefanie Schöne, Marcel Jurk, Mahdi Bagherpoor Helabad, Iris Dror, Isabelle Lebars, et al.. Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity. Nature Communications, 2016, 7 (1), ⟨10.1038/ncomms12621⟩. ⟨hal-03352071⟩
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