Table 1.

Overarching principles of vitamin D action in target cells.

VDR Binding Sites (The Cistrome): 2000-8000 1,25(OH)2D3-sensitive binding sites/genome whose number and location are determined by cell-type

Active Transcription Unit: The VDR/RXR heterodimer

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

VDR/RXR Binding Site Sequence (VDRE): Induction mediated by classic hexameric half-sites (AGGTCA) separated by 3 base pairs; Repression mediated by divergent sites

Mode of DNA Binding: Predominantly, but not exclusively, 1,25(OH)2D3-dependent

Modular Features: CRMs contain binding sites for multiple transcription factors that facilitate either independent or synergistic interaction

Epigenetic CRM Signatures: Defined by the dynamically regulated post-translational histone H3 and H4 modifications

VDR Cistromes are highly dynamic: Cistromes change during cell differentiation, maturation, and disease activation and thus have consequential effects on gene expression