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Updated: Jun 13, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Retinoic acid receptor gamma 2 interactions with vitamin D response elements
Nick J Koszewski1, Johann Herberth, Hartmut H Malluche
1University of Kentucky Medical Center, Division of Nephrology, Bone and Mineral Metabolism, 800 Rose Street, Lexington, KY 40536-0298, United States. nickkos1@iastate.edu
Retinoic acid receptor gamma 2 (RARgamma2) interacts with vitamin D response elements (VDREs), impacting vitamin D receptor (VDR) activity. This novel interaction fine-tunes transcriptional responses based on ligand availability and nuclear receptor expression.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- The vitamin D receptor (VDR) typically heterodimerizes with the retinoid X receptor (RXR) to bind vitamin D response elements (VDREs).
- Understanding VDR interactions is crucial for deciphering gene regulation by vitamin D.
Purpose of the Study:
- To identify novel VDR-interacting proteins on repressor VDREs.
- To investigate the functional impact of retinoic acid receptor gamma 2 (RARgamma2) on VDR-mediated transcription.
Main Methods:
- Modified yeast one-hybrid screen using a repressor VDRE.
- HeLa cell cDNA library screening.
- Reporter gene assays in COS-7 cells.
- Electrophoretic mobility shift assays (EMSAs).
Main Results:
- Retinoic acid receptor gamma 2 (RARgamma2) was identified as a protein that specifically interacts with VDREs.
- The A-domain of RARgamma2 is essential for its interaction with VDREs.
- Co-transfection of VDR and RARgamma2 attenuated transcriptional activation from an enhancer VDRE.
- A VDR/RARgamma2 complex was detected in nuclear extracts.
Conclusions:
- RARgamma2 exhibits a novel ability to interact with VDREs, independent of VDR.
- RARgamma2 can modulate VDR-mediated transcriptional activity.
- This interaction offers a new mechanism for fine-tuning vitamin D signaling based on cellular context and ligand availability.
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