Imperial College London
Alternate

Dr Antonio J Berlanga-Taylor

Faculty of Medicine, School of Public Health

Honorary Senior Research Fellow
 
 
 
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Contact

 

a.berlanga

 
 
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Location

 

47 Praed StreetSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Handel:2013:10.1186/1741-7015-11-163,
author = {Handel, AE and Sandve, GK and Disanto, G and Berlanga-Taylor, AJ and Gallone, G and Hanwell, H and Drabløs, F and Giovannoni, G and Ebers, GC and Ramagopalan, SV},
doi = {10.1186/1741-7015-11-163},
journal = {BMC Medicine},
title = {Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease},
url = {http://dx.doi.org/10.1186/1741-7015-11-163},
volume = {11},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Vitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associated with autoimmune diseases. We aimed to investigate VDR binding in primary CD4+ cells from healthy volunteers. METHODS: We extracted CD4+ cells from nine healthy volunteers. Each sample underwent VDR ChIP-seq. Our results were analyzed in relation to published ChIP-seq and RNA-seq data in the Genomic HyperBrowser. We used MEMEChIP for de novo motif discovery. 25-Hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry and samples were divided into vitamin D sufficient (25(OH)D ≥75 nmol/L) and insufficient/deficient (25(OH)D <75 nmol/L) groups. RESULTS: We found that the amount of VDR binding is correlated with the serum level of 25-hydroxyvitamin D (r = 0.92, P= 0.0005). In vivo VDR binding sites are enriched for autoimmune disease associated loci, especially when 25-hydroxyvitamin D levels (25(OH)D) were sufficient (25(OH)D ≥75: 3.13-fold, P<0.0001; 25(OH)D <75: 2.76-fold, P<0.0001; 25(OH)D ≥75 enrichment versus 25(OH)D <75 enrichment: P= 0.0002). VDR binding was also enriched near genes associated specifically with T-regulatory and T-helper cells in the 25(OH)D ≥75 group. MEME ChIP did not identify any VDR-like motifs underlying our VDR ChIP-seq peaks. CONCLUSION: Our results show a direct correlation between in vivo 25-hydroxyvitamin D levels and the number of VDR binding sites, although our sample size is relatively small. Our study further implicates VDR binding as important in gene-environment interactions underlying the development of autoimmunity and provides a biological rationale for 25-hydroxyvitamin D sufficiency being based at 75 nmol/L. Our results also suggest that VDR binding in response to physiological levels of vitamin D occurs predominantly in a VDR motif-independent m
AU  - Handel,AE
AU  - Sandve,GK
AU  - Disanto,G
AU  - Berlanga-Taylor,AJ
AU  - Gallone,G
AU  - Hanwell,H
AU  - Drabløs,F
AU  - Giovannoni,G
AU  - Ebers,GC
AU  - Ramagopalan,SV
DO  - 10.1186/1741-7015-11-163
PY  - 2013///
SN  - 1741-7015
TI  - Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/1741-7015-11-163
UR  - http://hdl.handle.net/10044/1/40377
VL  - 11
ER  -
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