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Patterns of genome-wide VDR locations.
PLoS One 2014; 9(4):e96105Plos

Abstract

The genome-wide analysis of the binding sites of the transcription factor vitamin D receptor (VDR) is essential for a global appreciation the physiological impact of the nuclear hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide analysis of lipopolysaccharide (LPS)-polarized THP-1 human monocytic leukemia cells via chromatin immunoprecipitation sequencing (ChIP-seq) resulted in 1,318 high-confidence VDR binding sites, of which 789 and 364 occurred uniquely with and without 1,25(OH)2D3 stimulation, while only 165 were common. We re-analyzed five public VDR ChIP-seq datasets with identical peak calling settings (MACS, version 2) and found, using a novel consensus summit identification strategy, in total 23,409 non-overlapping VDR binding sites, 75% of which are unique within the six analyzed cellular models. LPS-differentiated THP-1 cells have 22% more genomic VDR locations than undifferentiated cells and both cell types display more overlap in their VDR locations than the other investigated cell types. In general, the intersection of VDR binding profiles of ligand-stimulated cells is higher than those of unstimulated cells. De novo binding site searches and HOMER screening for binding motifs formed by direct repeats spaced by three nucleotides (DR3) suggest for all six VDR ChIP-seq datasets that these sequences are found preferentially at highly ligand responsive VDR loci. Importantly, all VDR ChIP-seq datasets display the same relationship between the VDR occupancy and the percentage of DR3-type sequences below the peak summits. The comparative analysis of six VDR ChIP-seq datasets demonstrated that the mechanistic basis for the action of the VDR is independent of the cell type. Only the minority of genome-wide VDR binding sites contains a DR3-type sequence. Moreover, the total number of identified VDR binding sites in each ligand-stimulated cell line inversely correlates with the percentage of peak summits with DR3 sites.

Authors+Show Affiliations

Department of Biosciences, University of Eastern Finland, Kuopio, Finland.Department of Biosciences, University of Eastern Finland, Kuopio, Finland.Department of Biosciences, University of Eastern Finland, Kuopio, Finland.Department of Biosciences, University of Eastern Finland, Kuopio, Finland.Department of Biosciences, University of Eastern Finland, Kuopio, Finland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24787735

Citation

Tuoresmäki, Pauli, et al. "Patterns of Genome-wide VDR Locations." PloS One, vol. 9, no. 4, 2014, pp. e96105.
Tuoresmäki P, Väisänen S, Neme A, et al. Patterns of genome-wide VDR locations. PLoS ONE. 2014;9(4):e96105.
Tuoresmäki, P., Väisänen, S., Neme, A., Heikkinen, S., & Carlberg, C. (2014). Patterns of genome-wide VDR locations. PloS One, 9(4), pp. e96105. doi:10.1371/journal.pone.0096105.
Tuoresmäki P, et al. Patterns of Genome-wide VDR Locations. PLoS ONE. 2014;9(4):e96105. PubMed PMID: 24787735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patterns of genome-wide VDR locations. AU - Tuoresmäki,Pauli, AU - Väisänen,Sami, AU - Neme,Antonio, AU - Heikkinen,Sami, AU - Carlberg,Carsten, Y1 - 2014/04/30/ PY - 2014/01/23/received PY - 2014/04/02/accepted PY - 2014/5/3/entrez PY - 2014/5/3/pubmed PY - 2015/1/23/medline SP - e96105 EP - e96105 JF - PloS one JO - PLoS ONE VL - 9 IS - 4 N2 - The genome-wide analysis of the binding sites of the transcription factor vitamin D receptor (VDR) is essential for a global appreciation the physiological impact of the nuclear hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide analysis of lipopolysaccharide (LPS)-polarized THP-1 human monocytic leukemia cells via chromatin immunoprecipitation sequencing (ChIP-seq) resulted in 1,318 high-confidence VDR binding sites, of which 789 and 364 occurred uniquely with and without 1,25(OH)2D3 stimulation, while only 165 were common. We re-analyzed five public VDR ChIP-seq datasets with identical peak calling settings (MACS, version 2) and found, using a novel consensus summit identification strategy, in total 23,409 non-overlapping VDR binding sites, 75% of which are unique within the six analyzed cellular models. LPS-differentiated THP-1 cells have 22% more genomic VDR locations than undifferentiated cells and both cell types display more overlap in their VDR locations than the other investigated cell types. In general, the intersection of VDR binding profiles of ligand-stimulated cells is higher than those of unstimulated cells. De novo binding site searches and HOMER screening for binding motifs formed by direct repeats spaced by three nucleotides (DR3) suggest for all six VDR ChIP-seq datasets that these sequences are found preferentially at highly ligand responsive VDR loci. Importantly, all VDR ChIP-seq datasets display the same relationship between the VDR occupancy and the percentage of DR3-type sequences below the peak summits. The comparative analysis of six VDR ChIP-seq datasets demonstrated that the mechanistic basis for the action of the VDR is independent of the cell type. Only the minority of genome-wide VDR binding sites contains a DR3-type sequence. Moreover, the total number of identified VDR binding sites in each ligand-stimulated cell line inversely correlates with the percentage of peak summits with DR3 sites. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24787735/Patterns_of_genome_wide_VDR_locations_ L2 - http://dx.plos.org/10.1371/journal.pone.0096105 DB - PRIME DP - Unbound Medicine ER -