Endocrine Abstracts

Vitamin D₃can be produced endogenously in UV-B exposed skin, but during winter months it should be supplemented via fortified foods or pills. The main physiological functions of vitamin D are the control of cellular metabolism and immunity via regulating calcium homeostasis and modulating the response of cells of the innate and adaptive immune system, respectively. The vitamin D metabolite 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) directly affects the epigenome and transcriptome of vitamin D receptor (VDR) target tissues and cell types. THP-1 human monocytes represent a model system that has studied most comprehensively for epigenome- and transcriptome-wide effects of 1,25(OH)₂D₃. These data are the basis of the chromatin model of vitamin D signaling describing how VDR’s spatio-temporal binding profile provides key insight into the pleiotropic action of vitamin D. Some 300 primary vitamin D target genes are regulated by VDR in concert with the pioneer transcription factors PU.1 and CEBPA and the chromatin organizer CTCF. Moreover, 1,25(OH)₂D₃directly affects histone markers of active promoter and enhancer regions as well as chromatin accessibility. Epigenome- and transcriptome-wide data obtained in context of the short-term vitamin D intervention study VitDbol (NCT02063334), where before and 24 h after a vitamin D₃bolus chromatin and RNA were prepared from peripheral blood mononuclear cells. Comparable principles of vitamin D signaling were confirmed in this in vivo model concerning target gene responses as well as changes in chromatin accessibility. Interestingly, the VitDbol study subjects showed a personalized response to vitamin D and could be distinguished into high, mid and low responders. In conclusion, short-term vitamin D supplementation studies represent a new type of safe in vivo investigations demonstrating that vitamin D and its metabolites have direct effects on the human epigenome and modulate the response of the transcriptome in a personalized fashion.