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Patterns of genome-wide VDR locations
Pauli Tuoresmäki1, Sami Väisänen1, Antonio Neme1
1Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
Plos One
|May 3, 2014
Summary
Genome-wide analysis of vitamin D receptor (VDR) binding sites reveals cell-type independent mechanisms. VDR
Area of Science:
- Molecular Biology
- Genomics
- Endocrinology
Background:
- The vitamin D receptor (VDR) mediates the physiological effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3).
- Understanding VDR's genome-wide binding is crucial for appreciating its biological roles.
Purpose of the Study:
- To perform a comprehensive genome-wide analysis of VDR binding sites across different cellular models.
- To investigate the impact of 1,25(OH)2D3 stimulation on VDR binding.
- To identify commonalities and differences in VDR binding mechanisms.
Main Methods:
- Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify VDR binding sites.
- Analysis of multiple public VDR ChIP-seq datasets with standardized peak calling.
- Novel consensus summit identification strategy and de novo motif discovery (DR3 sequences).
Main Results:
- A total of 23,409 non-overlapping VDR binding sites were identified across six datasets, with 75% unique to specific cellular models.
- Lipopolysaccharide (LPS)-polarized THP-1 cells showed increased VDR locations compared to undifferentiated cells.
- Direct repeat spaced by three nucleotides (DR3) motifs were preferentially found at ligand-responsive VDR loci, with a consistent relationship between VDR occupancy and DR3 presence.
Conclusions:
- The fundamental mechanism of VDR action is conserved across different cell types.
- A minority of VDR binding sites contain DR3 motifs.
- Ligand stimulation influences VDR binding patterns, with an inverse correlation between the number of binding sites and the percentage of DR3 motifs.
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