Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5507737 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2017 | 33 Pages |
Abstract
The transcription factor vitamin D receptor (VDR) is the exclusive nuclear target of the biologically active form of vitamin D (1,25(OH)2D3). In THP-1 human monocytes we obtained a highly accurate VDR cistrome after 2 and 24Â h ligand stimulation comprising >Â 11,600 genomic loci, 78% of which were detected exclusively after 24Â h. In contrast, a group of 510 persistent VDR sites occurred at all conditions and some 2100 VDR loci were only transiently occupied. Machine learning and statistical analysis as well as a comparison with the re-analyzed B cell VDR cistrome indicated a subgroup of 339 highly conserved persistent VDR sites that were suited best for describing vitamin D-triggered gene regulatory scenarios. The 1,25(OH)2D3-dependent transcriptome of THP-1 cells comprised 587 genes, 311 of which were primary targets with main functions in the immune system. More than 97% of the latter genes were located within 1,25(OH)2D3-modulated topologically associated domains (TADs). The number of persistent and transient VDR sites was found to be the main discriminator for sorting these TADs into five classes carrying vitamin D target genes involved in distinct biological processes. In conclusion, specific regulation of biological processes by vitamin D depends on differences in time-dependent VDR binding.
Keywords
FDRdirect repeat spaced by 3 nucleotides1,25(OH)2D3 or 1,25DDR3FAIRE-seqCTCFVDRMACSIGVTSSRNA-seqChIP-Seq1α,25-dihydroxyvitamin D3SOMchromatin immunoprecipitationTADRNA sequencingChIP sequencingfold changeformaldehyde-assisted isolation of regulatory elements sequencingtopologically associated domaintranscription start siteCCCTC-binding factorIntegrative Genomics Viewerfalse discovery rateSelf-organizing mapGene ontologyHomerCHiPGorillaVitamin D receptor
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Authors
Antonio Neme, Sabine Seuter, Carsten Carlberg,