The First Genome-wide View of Vitamin D Receptor Locations and Their Mechanistic Implications
CARSTEN CARLBERG1⇓, SABINE SEUTER2 and SAMI HEIKKINEN1
1Department of Biosciences, University of Eastern Finland, Kuopio, Finland
2Life Sciences Research Unit, University of Luxembourg, Luxembourg, Luxembourg
Correspondence to: Professor Carsten Carlberg, Department of Biosciences, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland. Tel: +358 403553062, Fax: +358 172811510, e-mail: carsten.carlberg at uef.fi
The transcription factor vitamin D receptor (VDR) is the nuclear sensor for the biologically most active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). The physiological actions of the VDR and its ligand are not only the well-known regulation of calcium and phosphorus uptake and transport controlling bone formation, but also their significant involvement in the control of immune functions and of cellular growth and differentiation. For a general understanding of the mechanisms of 1α,25(OH)2D3 signaling, it is essential to monitor the genome-wide location of VDR in relation to primary 1α,25(OH)2D3 target genes. Within the last months, two chromatin immunoprecipitation sequencing (ChIP-Seq) studies using cells of the hematopoietic system, lymphoblastoids and monocytes, were published. The reports indicated the existence of 2776 and 1820 1α,25(OH)2D3-stimulated VDR-binding sites, comparable numbers, of which, however, only 18.2% overlapped. The two studies were very different in their 1α,25(OH)2D3 treatment times (36 h versus 40 min), but showed consensus in identifying response elements formed by a direct repeat of two hexameric binding sites with three intervening nucleotide (DR3) as major DNA contact sites of the VDR. Interestingly, when analyzed in the same way, both reports indicated that within 100 bp of their VDR ChIP-Seq peak summits only fewer than 40% contain a DR3-type response element. This review provides a detailed comparison of the insights obtained from both ChIP-Seq studies.
Figure 1. 1α,25(OH)2D3 target gene comparison. Up-regulated 1α,25(OH)2D3 target genes from three different microarray datasets were compared:
THP-1 cells after short [4 h, red (8)] or long (24 h, purple, unpublished data) 1α,25(OH)2D3 treatment and in lymphoblastoid cell lines (LCLs) after
long [36 h, blue (39)] 1α,25(OH)2D3 stimulation. Numbers of genes in each overlapping or unique gene set are given within the Venn diagram.
Note that the circle sizes and degrees of overlap are only approximations.
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See also Vitamin D Life
Molecular Approaches for Optimizing Vitamin D (one size does not fit all) – Carlberg Nov 2015
Vitamin D Receptor category listing hasVitamin D ==> Calcidiol = measured Vitamin D ==> Calcitriol ==> Vitamin D Receptor ==> Cell
Thus you can have a good measured level of vitamin D, but the Cell does not get as much due to poor Vitamin D Receptor
Vitamin D Receptor is in the far right of the chart
Click on chart for details
Difficult to know if your Vitamin D Receptors are workly properly - no simple test
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