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© Research
Publication : The Journal of biological chemistry

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of biological chemistry - 07 Apr 2016

Tesikova M, Dezitter X, Nenseth HZ, Klokk TI, Mueller F, Hager GL, Saatcioglu F

Link to Pubmed [PMID] – 27056330

J. Biol. Chem. 2016 Apr;

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.

http://www.ncbi.nlm.nih.gov/pubmed/27056330