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Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element.

Authors
  • Tesikova, Martina1
  • Dezitter, Xavier1
  • Nenseth, Hatice Z1
  • Klokk, Tove I1
  • Mueller, Florian2
  • Hager, Gordon L3
  • Saatcioglu, Fahri4
  • 1 From the Department of Biosciences, University of Oslo, 0316 Oslo, Norway. , (Norway)
  • 2 Computational Imaging and Modeling Unit, Institut Pasteur, 75015 Paris, France. , (France)
  • 3 Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, and.
  • 4 From the Department of Biosciences, University of Oslo, 0316 Oslo, Norway, Institute for Cancer Genetics and Informatics, Division of Cancer and Surgery, Oslo University Hospital, 0310 Oslo, Norway [email protected] , (Norway)
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
May 27, 2016
Volume
291
Issue
22
Pages
11899–11910
Identifiers
DOI: 10.1074/jbc.M115.684480
PMID: 27056330
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Transcription factor (TF) recruitment to chromatin is central to activation of transcription. TF-chromatin interactions are highly dynamic, which are evaluated by recovery half time (t1/2) in seconds, determined by fluorescence recovery experiments in living cells, and chromatin immunoprecipitation (ChIP) analysis, measured in minutes. These two states are related: the larger the t1/2, the longer the ChIP occupancy resulting in increased transcription. Here we present data showing that this relationship does not always hold. We found that histone deacetylase inhibitors (HDACis) significantly increased t1/2 of green fluorescent protein (GFP) fused androgen receptor (AR) on a tandem array of positive hormone response elements (HREs) in chromatin. This resulted in increased ChIP signal of GFP-AR. Unexpectedly, however, transcription was inhibited. In contrast, the GFP-fused glucocorticoid receptor (GR), acting through the same HREs, displayed a profile consistent with current models. We provide evidence that these differences are mediated, at least in part, by HDACs. Our results provide insight into TF action in living cells and show that very closely related TFs may trigger significantly divergent outcomes at the same REs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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