New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
Abstract
:1. Background and Review Rationale
2. Transcriptional Mechanism of Action of 1,25(OH)2D3
3. Analogues of Vitamin D
4. Pharmacology of Vitamin D Analogues
5. New Insights into Transcriptional Activation of Vitamin D
6. Current Advances in Transcriptional Regulation
7. Recent Work at the Frontier for Enhancing Vitamin D Analogue SAR Potential
8. Vitamin D Analogues
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Active Transcription Unit for Induction: The VDR/RXR heterodimer |
VDR Binding Sites (The VDR Cistrome): 2000–8000 1,25(OH)2D3-sensitive binding sites/genome whose number and location are chromatin dependent and a function of cell-type |
Mode of DNA Binding: Predominantly, but not exclusively, 1,25(OH)2D3-dependent |
VDR/RXR Binding Site Sequence (VDRE): Induction mediated by classic hexameric half-sites (AGGTCA) separated by 3 base pairs; Repression mediated by divergent sites |
Distal Binding Site Locations: Dispersed in cis-regulatory modules (CRMs or enhancers) across the genome; located in a cell-type specific manner near promoters, but predominantly within introns and distal intergenic regions; frequently located in clusters of elements |
Epigenetic CRM Signatures: Defined by the dynamically regulated post-translational histone H3 and H4 modifications |
Modular Features of CRMs: Contain binding sites for multiple transcription factors that facilitate either independent or synergistic interaction |
VDR Cistromes: Dynamic alterations in the cellular epigenome during differentiation, maturation, and disease provoke changes to the VDR cistrome that qualitatively and quantitatively affect the vitamin D regulated transcriptome |
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Pike, J.W.; Meyer, M.B. New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues. Int. J. Mol. Sci. 2021, 22, 12352. https://doi.org/10.3390/ijms222212352
Pike JW, Meyer MB. New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues. International Journal of Molecular Sciences. 2021; 22(22):12352. https://doi.org/10.3390/ijms222212352
Chicago/Turabian StylePike, John Wesley, and Mark B. Meyer. 2021. "New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues" International Journal of Molecular Sciences 22, no. 22: 12352. https://doi.org/10.3390/ijms222212352