A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution
| Autor: | Julian C. Knight, Giulio Disanto, George C. Ebers, Antonio J. Berlanga, Corey T. Watson, Chris P. Ponting, Matthew R. Lincoln, Gavin Giovannoni, Lahiru Handunnetthi, S M Orton, Amy M Burrell, Julia M. Morahan, Adam E. Handel, Narelle J. Maugeri, Sreeram V. Ramagopalan, Andreas Heger |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Chromatin Immunoprecipitation
Multiple Sclerosis Single-nucleotide polymorphism Biology Calcitriol receptor Autoimmune Diseases Evolution Molecular 03 medical and health sciences 0302 clinical medicine Crohn Disease Genetics Vitamin D and neurology Humans Vitamin D Gene Transcription factor Genetics (clinical) 030304 developmental biology Protein Tyrosine Phosphatase Non-Receptor Type 2 0303 health sciences Binding Sites Research Sequence Analysis DNA Diabetes Mellitus Type 1 Interferon Regulatory Factors Receptors Calcitriol Human genome Chromatin immunoprecipitation 030217 neurology & neurosurgery Vitamin D receptor binding Genome-Wide Association Study Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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