A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.

By S. Ramagopalan, Andreas Heger, A. J. Berlanga, N. Maugeri, M. Lincoln, Amy M. Burrell, L. Handunnetthi, A. Handel, G. Disanto, S. Orton and 6 more. Genome Research, 2010

876 citations recorded by the source corpus.

Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8, associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for example, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among individuals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases.

Subfields: Genetics, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/0a1d96377bee2fcd23aa79c6b6bd04e38bd83dcd

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In Genetics

1. D. Leung
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In Pathology and Forensic Medicine

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Citations in the corpus

• Vitamin D Inhibits Monocyte/macrophage Pro-inflammatory Cytokine Production by Targeting Mitogen-Activated Protein Kinase Phosphatase 1 (2012, background): “The far upstream location of the putative VDRE in murine MKP-1 promoter is not surprising because genome-wide mapping of VDRE have indicated that VDREs are predominantly located in introns and intergenic intervals (7).”
• Vitamin D Metabolism, Mechanism of Action, and Clinical Applications (2014, positive): “In a separate study with human lymphoblastoid cell lines treated with 1,25(OH)2D, 2,776 VDR binding sites were found altering the expression of 229 genes (Ramagopalan et al., 2010).”
• The MEME Suite (2015, methodology): “) For this case study, we use ChIP-seq data for the nuclear vitamin D receptor protein VDR (37).”
• Vitamin D for Health: A Global Perspective (2013, neutral): “These data indicate that intrinsic activation of 25(OH)D3 to 1,25(OH)2D3 occurs in DCs from patients with CD and provides evidence that higher serum 25(OH)D3 levels can potentially modulate DC function in CD.182 Although several studies reported the immunomodulatory effects of vitamin D on biologica”
• Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. (2013, background): “Chromatin immunoprecipitation studies have helped defined where ligand-dependent transcription occurs (Ramagopalan et al., 2010), but to date these data have been based on non-neuronal tissue.”