title: Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system.
abstract: Vitamin D(3) belongs to the few nutritional compounds that has, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. The relation of thousands of genomic VDR-binding sites to a few hundred primary 1,25(OH)(2)D(3) target genes is still largely unresolved. We studied chromatin domains containing genes for the adhesion molecules CD97 and LRRC8A, the glucose transporter SLC37A2 and the coactivator NRIP1. These domains vary significantly in size (7.3 to 956 kb) but contain each one major VDR-binding site. In monocytic cells these four sites are associated with open chromatin and occupied by VDR, while in macrophage-like cells only the sites of LRRC8A, SLC37A2 and NRIP1 are accessible and receptor bound. The VDR site of CD97 does, in contrast to the three other loci, not carry any DR3-type binding sequence. CD97, LRRC8A, SLC37A2 and NRIP1 are early responding 1,25(OH)(2)D(3) target genes in monocytic cells, while in macrophage-like cells they respond less and, in part, delayed. In primary human peripheral blood mononuclear cells from 71 prediabetic subjects of a vitamin D(3) intervention study (VitDmet) CD97, LRRC8A, SLC37A2 and NRIP1 can be used as transcriptomic biomarkers for classifying human individuals for their possible benefit from vitamin D(3) supplementation. In particular, NRIP1 exceeds the potential of the previously identified marker CD14 by more than 40% and seems to be a well-suited molecular marker for the vitamin D(3) status in the hematopoietic system.
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Julia
authors.initials: J
authors.lastname: Wilfinger
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Seuter
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Tomi-Pekka
authors.initials: TP
authors.lastname: Tuomainen
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Jyrki K
authors.initials: JK
authors.lastname: Virtanen
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Voutilainen
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Nurmi
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Vanessa D F
authors.initials: VD
authors.lastname: de Mello
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70211 Kuopio, Finland. Electronic address: carsten.carlberg@uef.fi.
authors.forename: Carsten
authors.initials: C
authors.lastname: Carlberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D017920:Antiporters / Q000235:genetics*; D001665:Binding Sites; D015415:Biomarkers; D002117:Calcitriol / Q000494:pharmacology; D002762:Cholecalciferol / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D000078723:Nuclear Receptor Interacting Protein 1; D011236:Prediabetic State / Q000097:blood / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017920:Antiporters; D015415:Biomarkers; D002843:Chromatin; C485976:LRRC8A protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D018167:Receptors, Calcitriol; C569995:Slc37a2 protein, human; C579457:VDR protein, human; D019014:fas Receptor; D002762:Cholecalciferol; D002117:Calcitriol
keywords: Biomarker; Chromatin; Gene regulation; Primary vitamin D target genes; Vitamin D receptor; Vitamin D(3); Vitamin D(3) supplementation