title: What do we learn from the genome-wide perspective on vitamin D3?
abstract: Vitamin D3 insufficiency is associated with a number of diseases, such as cancer and autoimmune disorders. This important medical problem leads to the question, whether an insight into the genome-wide actions of the transcription factor vitamin D receptor (VDR) and its high affinity ligand 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) can help in a more global appreciation of the physiological impact of vitamin D3. Chromatin immunoprecipitation sequencing (ChIP-seq) studies in 6 human cell culture models demonstrated 1,000 to 10,000 genomic VDR binding sites per cell type that sum-up to more than 23,000 non-overlapping loci of the receptor. After ligand stimulation VDR associates with many new binding loci, of which the most important have a higher rate of DR3-type VDR binding sequences than average sites. On the majority of latter VDR interacts directly or indirectly with genomic DNA in a presently uncharacterized fashion. Formaldehyde-assisted isolation of regulatory elements sequencing (FAIRE-seq) monitors the dynamically opening chromatin regions after 1,25(OH)2D3 stimulation. The integration of ChIP-seq and FAIRE-seq data combined with a screening for DR3-type sequences facilitates the identification of key VDR binding sites and primary 1,25(OH)2D3 target genes. Recent results of the FANTOM5 project strongly suggest a shift from in vitro cell culture experiments to primary human cells stimulated in vivo. First results suggest that both the number of genome-wide VDR binding sites and the expression of VDR target genes correlate with vitamin D status of the studied human individuals. In conclusion, a genome-wide overview provides a broader basis for addressing vitamin D's role in health and disease.
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland carsten.carlberg@uef.fi.
authors: Carsten
authors: C
authors: Carlberg
mesh_terms: D002478:Cells, Cultured; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D015894:Genome, Human; D006801:Humans; D018167:Receptors, Calcitriol / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D002762:Cholecalciferol
keywords: 1,25(OH)2D3; ChIP-seq; Vitamin D insuffiency; genome-wide research; review; vitamin D receptor