Vitamin D Genomics: From In Vitro to In Vivo
Self archived versionpublished version
MetadataShow full item record
CitationCarlberg, Carsten. (2018). Vitamin D Genomics: From In Vitro to In Vivo. FRONTIERS IN ENDOCRINOLOGY, 9, 250. 10.3389/fendo.2018.00250.
The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the exclusive high-affinity ligand of the vitamin D receptor (VDR), a transcription factor with direct effects on gene expression. Transcriptome- and epigenome-wide data obtained in THP-1 human monocytes are the basis of the chromatin model of vitamin D signaling. The model describes, how VDR’s spatio-temporal binding profile provides key insight into the pleiotropic action of vitamin D. The transcription of some 300 primary target genes is significantly modulated through the action of genomic VDR binding sites in concert with the pioneer transcription factor PU.1 and the chromatin organizer CTCF. In parallel, the short-term vitamin D intervention study VitDbol (NCT02063334) was designed, in order to extrapolate insight into vitamin D signaling from in vitro to in vivo. Before and 24 h after a vitamin D3 bolus chromatin and RNA were prepared from peripheral blood mononuclear cells for epigenome- and transcriptome-wide analysis. The study subjects showed a personalized response to vitamin D and could be distinguished into high, mid, and low responders. Comparable principles of vitamin D signaling were identified in vivo and in vitro concerning target gene responses as well as changes in chromatin accessibility. 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.
Subjectsvitamin D vitamin D receptor vitamin D target genes vitamin D intervention trial chromatin epigenome immune system
Link to the original itemhttp://dx.doi.org/10.3389/fendo.2018.00250
PublisherFrontiers Media SA
- Terveystieteiden tiedekunta 
Showing items related by title, author, creator and subject.
Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells Vukić, Maja; Neme, Antonio; Seuter, Sabine; Saksa, Noora; de Mello, Vanessa D. F.; Nurmi, Tarja; Uusitupa, Matti; Tuomainen, Tomi-Pekka (Public Library of Science (PLoS), 2015)Vitamin D3 has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using ...info:eu-repo/semantics/article
Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes Aatsinki, SM; Elkhwanky, MS; Kummu, O; Karpale, M; Buler, M; Viitala, P; Rinne, V; Mutikainen, M; Tavi, P; Franko, A; Wiesner, RJ; Chambers, KT; Finck, BN; Hakkola, J (American Diabetes Association, 2019)Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation–responsive mechanisms regulate vitamin D metabolism. Both fasting ...Tieteelliset aikakauslehtiartikkelit
Carlberg Carsten (Elsevier BV, 2017)The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the ...info:eu-repo/semantics/article