Biochemical and Biophysical Research Communications
Dimerization modulates the activity of the orphan nuclear receptor ERRγ☆
Section snippets
Materials and methods
Plasmid constructions and site-directed mutagenesis. pCMX-ERRα, pCMX-ERRβ, and pCMX-ERRγ expression plasmids were generous gifts from Dr. Vincent Giguère (McGill University Health Center, Montréal, Quebec, Canada). pCMX-FLAG was generated by cloning a double stranded oligonucleotide encoding FLAG to the pCMX-PL1 vector kindly provided by Dr. Ronald Evans (Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA). pCMX-FLAG-ERRγΔNTD contains residues 88–435 of
Ligand-binding domain mediates ERRγ homodimerization
When the binding of ERRγ to ERRE and ERE response elements was examined in EMSA experiments, two protein–DNA complexes were reproducibly detected (Fig. 1). Both complexes were supershifted when an antibody recognizing the FLAG-epitope of the FLAG-ERRγ protein was added to the binding reaction (Fig. 1B). This result suggested that ERRγ binds DNA both as a monomer and as a homodimer. To study this further, a deletion mutant (ERRγΔNTD) lacking most of the amino-terminal domain was created.
Acknowledgements
Professor Olli A. Jänne is warmly thanked for support and for providing excellent research facilities. Drs. Ronald Evans, Vincent Giguère, Pekka Kallio, and Thomas Perlmann are acknowledged for providing plasmids. This work was supported by grants from the Medical Research Council (Academy of Finland), the Sigrid Juselius Foundation, and Biocentrum Helsinki.
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Abbreviations: 4OHT, 4-hydroxytamoxifen; AF2, activation function-2; DBD, DNA-binding domain; DES, diethylstilbestrol; ERE, estrogen receptor response element; ERR, estrogen-related receptor; ERRE, estrogen-related receptor’s response element; LBD, ligand-binding domain; NR, nuclear receptor; NTD, aminoterminal domain; PGC-1, peroxisome proliferator-activated receptor coactivator-1.