Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening.
The vitamin D receptor (VDR) is a transcription factor that mediates the genomic effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide there are several thousand binding sites and hundreds of primary 1,25(OH)2D3 target genes, but their functional relation is largely elusive. In this study,...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3999108?pdf=render |
| _version_ | 1819079864684118016 |
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| author | Sabine Seuter Antonio Neme Carsten Carlberg |
| author_facet | Sabine Seuter Antonio Neme Carsten Carlberg |
| author_sort | Sabine Seuter |
| collection | DOAJ |
| description | The vitamin D receptor (VDR) is a transcription factor that mediates the genomic effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide there are several thousand binding sites and hundreds of primary 1,25(OH)2D3 target genes, but their functional relation is largely elusive. In this study, we used ChIA-PET data of the transcription factor CTCF in combination with VDR ChIP-seq data, in order to map chromatin domains containing VDR binding sites. In total, we found 1,599 such VDR containing chromatin domains and studied in THP-1 human monocytic leukemia cells four representatives of them. Our combined ChIP-seq and FAIRE-seq time course data showed that each of these four domains contained a master VDR binding site, where an increase of VDR binding pairs with 1,25(OH)2D3-promoted chromatin opening and the presence of a highly significant DR3-type sequence below the peak summit. These sites differed in their relative VDR binding but not in their kinetics, while other loci either had a weaker and delayed VDR association or could not be confirmed at all. All studied chromatin domains contained at least one primary 1,25(OH)2D3 target gene demonstrating a characteristic slope of mRNA increase, while neighboring genes responded delayed, if at all. In conclusion, the observation of ligand-inducible VDR binding and chromatin opening combined with a DR3-type sequence highlighted genome-wide 160 VDR loci that have within their chromatin domain a more than 4-fold increased likelihood to identify a primary 1,25(OH)2D3 target gene than in the vicinity of other genomic VDR binding sites. |
| first_indexed | 2024-12-21T19:35:46Z |
| format | Article |
| id | doaj.art-b12b6de9b61f49868197b0ab45d754d5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T19:35:46Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b12b6de9b61f49868197b0ab45d754d52022-12-21T18:52:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9618410.1371/journal.pone.0096184Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening.Sabine SeuterAntonio NemeCarsten CarlbergThe vitamin D receptor (VDR) is a transcription factor that mediates the genomic effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide there are several thousand binding sites and hundreds of primary 1,25(OH)2D3 target genes, but their functional relation is largely elusive. In this study, we used ChIA-PET data of the transcription factor CTCF in combination with VDR ChIP-seq data, in order to map chromatin domains containing VDR binding sites. In total, we found 1,599 such VDR containing chromatin domains and studied in THP-1 human monocytic leukemia cells four representatives of them. Our combined ChIP-seq and FAIRE-seq time course data showed that each of these four domains contained a master VDR binding site, where an increase of VDR binding pairs with 1,25(OH)2D3-promoted chromatin opening and the presence of a highly significant DR3-type sequence below the peak summit. These sites differed in their relative VDR binding but not in their kinetics, while other loci either had a weaker and delayed VDR association or could not be confirmed at all. All studied chromatin domains contained at least one primary 1,25(OH)2D3 target gene demonstrating a characteristic slope of mRNA increase, while neighboring genes responded delayed, if at all. In conclusion, the observation of ligand-inducible VDR binding and chromatin opening combined with a DR3-type sequence highlighted genome-wide 160 VDR loci that have within their chromatin domain a more than 4-fold increased likelihood to identify a primary 1,25(OH)2D3 target gene than in the vicinity of other genomic VDR binding sites.http://europepmc.org/articles/PMC3999108?pdf=render |
| spellingShingle | Sabine Seuter Antonio Neme Carsten Carlberg Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. PLoS ONE |
| title | Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. |
| title_full | Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. |
| title_fullStr | Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. |
| title_full_unstemmed | Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. |
| title_short | Characterization of genomic vitamin D receptor binding sites through chromatin looping and opening. |
| title_sort | characterization of genomic vitamin d receptor binding sites through chromatin looping and opening |
| url | http://europepmc.org/articles/PMC3999108?pdf=render |
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