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What do we learn from the genome-wide perspective on vitamin D3?
Anticancer Res 2015; 35(2):1143-51AR

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+Show Affiliations

School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland carsten.carlberg@uef.fi.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25667505

Citation

Carlberg, Carsten. "What Do We Learn From the Genome-wide Perspective On Vitamin D3?" Anticancer Research, vol. 35, no. 2, 2015, pp. 1143-51.
Carlberg C. What do we learn from the genome-wide perspective on vitamin D3? Anticancer Res. 2015;35(2):1143-51.
Carlberg, C. (2015). What do we learn from the genome-wide perspective on vitamin D3? Anticancer Research, 35(2), pp. 1143-51.
Carlberg C. What Do We Learn From the Genome-wide Perspective On Vitamin D3. Anticancer Res. 2015;35(2):1143-51. PubMed PMID: 25667505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - What do we learn from the genome-wide perspective on vitamin D3? A1 - Carlberg,Carsten, PY - 2015/2/11/entrez PY - 2015/2/11/pubmed PY - 2015/4/10/medline KW - 1,25(OH)2D3 KW - ChIP-seq KW - Vitamin D insuffiency KW - genome-wide research KW - review KW - vitamin D receptor SP - 1143 EP - 51 JF - Anticancer research JO - Anticancer Res. VL - 35 IS - 2 N2 - 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. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/25667505/What_do_we_learn_from_the_genome_wide_perspective_on_vitamin_D3 L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=25667505 DB - PRIME DP - Unbound Medicine ER -