Báo cáo khoa học: Domains of ERRcthat mediate homodimerization and interaction with factors stimulating DNA binding

The DNA Binding Characteristics of Estrogen Receptor-Related Receptor γ

Authors: Moritz Hentschke, Ute Süsens, and Uwe Borgmeyer

Field: Molecular Neurobiology

Document Content:
This study investigates the DNA binding properties of the estrogen receptor-related receptor γ (ERRγ), an orphan member of the nuclear receptor superfamily. The research explores how ERRγ mediates homodimerization and interacts with factors that enhance DNA binding. Experiments utilizing electrophoretic mobility shift assays (EMSAs) and deletion constructs reveal that ERRγ binds DNA as a homodimer to various response elements, including direct repeats (DR-0) and extended half-sites. The study identifies that the ligand-binding domain (LBD) and the hinge region play crucial roles in DNA-independent dimerization. Furthermore, it highlights the necessity of additional factors present in serum and cellular extracts for efficient DNA binding of bacterial-expressed ERRγ. The research also characterizes the stimulating activity of these factors, demonstrating their heat sensitivity and their association with proteins. The findings suggest that a specific sequence element in the hinge region is essential for this stimulating effect, and the LBD is not required for activation. The study concludes that ERRγ binds preferentially as a dimer to DNA and that at least two dimerization modules are involved in this process.

Detailed Table of Contents:

• Introduction to Nuclear Receptors and ERRγ
• DNA Binding Specificity of ERRγ
• Role of Serum and Cellular Factors in ERRγ DNA Binding
• Characterization of the Stimulating Activity
• Localization of the Stimulating Effect to the Hinge Region
• Dimerization Properties of ERRγ
• DNA Binding of C-terminal Deletion Mutants
• Dimerization Function of ERRγ
• Discussion and Future Directions