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[Gene structure and transcriptional regulation of vitamin A, D binding proteins and nuclear receptors]
1Institute of Molecular and Cellular Biosciences, University of Tokyo.
Abstract:
Vitamin A and D play an important role in many biological processes including cell differentiation, proliferation and bone metabolism. These effects are believed to be mediated by specific nuclear receptors such as retinoic acid receptors (RARs) or vitamin D receptor (VDR), that regulate the transcription of a particular set of target genes. Hetero-dimers of RAR or VDR to retinoid X receptors (RXRs) bind target enhancer elements in their gene promoters. The target enhancer elements are referred as RA response elements (RAREs) or vitamin D response elements (VDREs), and composed of two hexamer core motife. DNA-bound RAR/VDR control transcription in a ligand-binding dependent way in co-operation with a multiprotein complex containing RNA polymerase II and a series of auxiliary factors, TFIIA, B, D, E, F and H. During process of ligand-induced transactivation by nuclear receptors, nuclear coactivators interacting with the AF-2 including ligand binding domain (LBD) seems to be involved. Several transcriptional coactivators and corepressors have been recently identified, and their function is currently under investigation.
Insights
Vitamins A and D regulate gene transcription via nuclear receptors like retinoic acid receptors (RARs) and vitamin D receptor (VDR). These receptors, along with retinoid X receptors (RXRs), control cell processes by binding to DNA response elements.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Context:
- Vitamins A and D are crucial for cell differentiation, proliferation, and bone metabolism.
- Their biological effects are mediated by nuclear receptors, specifically retinoic acid receptors (RARs) and the vitamin D receptor (VDR).
- These receptors regulate gene transcription by binding to specific DNA sequences.
Purpose:
- To elucidate the molecular mechanisms by which Vitamins A and D influence biological processes.
- To understand the role of nuclear receptors (RARs, VDR, RXRs) in gene regulation.
- To investigate the involvement of coactivators and corepressors in ligand-induced transactivation.
Summary:
- Vitamins A and D exert their functions through nuclear receptors (RARs, VDR) that form heterodimers with retinoid X receptors (RXRs).
- These complexes bind to specific DNA elements (RAREs, VDREs) to control gene transcription.
- Ligand binding to the receptors modulates transcriptional activity via interactions with coactivators and corepressors.
Impact:
- Provides insights into the fundamental mechanisms of vitamin-mediated gene regulation.
- Highlights the central role of nuclear receptor complexes in cellular processes.
- Establishes a foundation for further research into transcriptional coactivators and corepressors.