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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Requirements for transcriptional regulation by the orphan nuclear receptor ERRgamma.

Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor lacking identified natural ligands. We have addressed the requirements for ERRgamma-mediated gene regulation. ERRgamma transactivates constitutively reporter genes driven by ERR response elements (ERREs) or estrogen response elements (EREs). The activation depends on an intact DNA-binding domain (DBD) and activation function-2 (AF2). ERRgamma-mediated transactivation is further enhanced by peroxisome proliferator-activated receptor coactivator-1. Interestingly, ligand-binding domain (LBD) mutations predicted to either enlarge or diminish the putative ligand-binding pocket have no effect on the transcriptional activity implying that ERRgamma activity does not depend on any ligands. Antiestrogens 4OH-tamoxifen (4OHT) and 4-hydroxytoremifene (4OHtor) inhibit the ability of ERR to transactivate ERRE and ERE reporters. In contrast, ERRgamma activates transcription at AP-1 sites in the presence of 4OHT and 4OHtor. Thus, the transcriptional activity of ERRgamma seems not to require ligand binding but is modulated by binding of certain small synthetic ligands.[1]

References

  1. Requirements for transcriptional regulation by the orphan nuclear receptor ERRgamma. Huppunen, J., Wohlfahrt, G., Aarnisalo, P. Mol. Cell. Endocrinol. (2004) [Pubmed]
 
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