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Retinoid X and retinoic acid receptors interact with transcription factor II-B by distinct mechanisms
1Division of Biological Sciences, University of California at Davis, 95616, USA.
Abstract:
Nuclear hormone receptors are believed to modulate target gene expression by interacting with the general transcriptional machinery of the cell. We demonstrate here that two otherwise closely related members of the nuclear hormone receptor family, retinoid acid receptors (RARs) and retinoid X receptors (RXRs), exhibit significant differences in their interactions with the transcriptional machinery. RARs display a strong constitutive interaction with transcription factor II-B (TFIIB) that requires the TFIIB C-terminus, whereas RXR exhibits a weaker, hormone-stimulated interaction with the TFIIB that maps outside of the TFIIB C-terminus. Use of a dominant-negative mutant of TFIIB suggests that the TFIIB interaction is essential for full transcriptional activation by RXR.
Insights
Nuclear hormone receptors like retinoid acid receptors (RARs) and retinoid X receptors (RXRs) interact differently with transcription factor II-B (TFIIB). This TFIIB interaction is crucial for RXR
Area of Science:
- Molecular Biology
- Gene Regulation
- Cellular Biology
Background:
- Nuclear hormone receptors regulate gene expression by interacting with cellular transcriptional machinery.
- Retinoid acid receptors (RARs) and retinoid X receptors (RXRs) are closely related nuclear hormone receptors.
Purpose of the Study:
- To investigate the distinct interactions of RARs and RXRs with the general transcriptional machinery.
- To elucidate the role of transcription factor II-B (TFIIB) in retinoid receptor-mediated transcription.
Main Methods:
- Comparative analysis of RAR and RXR interactions with TFIIB.
- Mapping of interaction domains on TFIIB.
- Utilizing dominant-negative TFIIB mutants to assess functional significance.
Main Results:
- RARs exhibit a strong, constitutive interaction with TFIIB, dependent on the TFIIB C-terminus.
- RXRs show a weaker, hormone-stimulated interaction with TFIIB, mapping outside the C-terminus.
- TFIIB interaction is essential for full transcriptional activation by RXR.
Conclusions:
- RARs and RXRs display differential mechanisms of interaction with the transcriptional machinery.
- The specific interaction of RXR with TFIIB is critical for its transcriptional activity.
- Findings highlight distinct functional roles of related nuclear hormone receptors in gene regulation.