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- Title
The structural basis of direct glucocorticoid-mediated transrepression.
- Authors
Hudson, William H; Youn, Christine; Ortlund, Eric A
- Abstract
A newly discovered negative glucocorticoid response element (nGRE) mediates DNA-dependent transrepression by the glucocorticoid receptor (GR) across the genome and has a major role in immunosuppressive therapy. The nGRE differs dramatically from activating response elements, and the mechanism driving GR binding and transrepression is unknown. To unravel the mechanism of nGRE-mediated transrepression by the GR, we characterized the interaction between GR and an nGRE in the thymic stromal lymphopoietin (TSLP) promoter. We show using structural and mechanistic approaches that nGRE binding is a new mode of sequence recognition by human GR and that nGREs prevent receptor dimerization through a unique GR-binding orientation and strong negative cooperativity, ensuring the presence of monomeric GR at repressive elements.
- Subjects
GLUCOCORTICOID receptors; THYMIC stromal lymphopoietin; GENOMES; IMMUNOSUPPRESSIVE agents; DIMERIZATION
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 1, p53
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2456