Synthetic Chemical Probes That Dissect Vitamin D Activities

Vitamin
D3 metabolites are capable of controlling gene
expression in mammalian cells through two independent pathways: vitamin
D receptor (VDR) and sterol regulatory element-binding protein (SREBP)
pathways. In the present study, we dissect the complex biological
activity of vitamin D by designing synthetic vitamin D3 analogs specific for VDR or SREBP pathway, i.e., a VDR activator
that lacks SREBP inhibitory activity, or an SREBP inhibitor devoid
of VDR activity. These synthetic vitamin D probes permitted identification
of one of the vitamin D-responsive genes, Soat1,
as an SREBP-suppressed gene. The chemical probes developed in the
present study may prove useful in dissecting the intricate interplay
of vitamin D actions, thereby providing insights into how vitamin
D target genes are regulated.