OPEN IN READ APP
JOURNAL ARTICLE
REVIEW

What do we learn from the genome-wide perspective on vitamin D3?

Carsten Carlberg
Anticancer Research 2015, 35 (2): 1143-51
25667505
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.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
25667505
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"