In vivo response of the human epigenome to vitamin D: A Proof-of-principle study. Issue 180 (June 2018)

• Record Type: Journal Article
• Authors: Carlberg, Carsten; Seuter, Sabine; Nurmi, Tarja; Tuomainen, Tomi-Pekka; Virtanen, Jyrki K.; Neme, Antonio
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 180(2017)
• Page Start: 142
• Page End: 148
• Publication Date: 2018-06
• Subjects: 1, 25(OH)2D3 1α, 25-dihydroxyvitamin D3 -- 25(OH)D3 25-hydroxyvitamin D3 -- APOO apolipoprotein O -- CLIP4 CAP-Gly domain containing linker protein family member 4 -- EHMT2 euchromatic histone lysine methyltransferase 2 -- FAIRE-seq formaldehyde-assisted isolation of regulatory elements sequencing -- FBF1 Fas binding factor 1 -- FDR false discovery rate -- FE fold enrichment -- FKBPL FK506 binding protein like -- GEO Gene Expression Omnibus -- HLA human leukocyte antigen -- IGV Integrative Genomics Viewer -- MAPK8 mitogen-activated protein kinase 8 -- MHC major histocompatibility complex -- PBMC peripheral blood mononuclear cell -- SOAT1 sterol O-acyltransferase 1 -- SOM self-organizing map -- SUN1 Sad1 and UNC84 domain containing 1 -- TBCCD1 TBCC domain containing 1 -- TNF tumor necrosis factor -- TSS transcription start site -- VDR vitamin D receptor -- WRAP73 WD repeat containing, antisense to TP73; Vitamin D3 -- Epigenome -- Vitamin D3 -- Bolus supplementation -- Accessible chromatin -- PBMCs -- FAIRE-seq -- SOM -- HLA cluster; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.01.002
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: One individual was exposed three times every 28 days to an oral bolus (2000 μg) of vitamin D3 . At nine time points epigenome-wide chromatin accessibility was assessed by FAIRE-seq. 853 most prominent genomic loci were classified into early, delayed and non-responding. A rather minor rise in 25(OH)D3 serum levels results in significant changes of the epigenome. Abstract: In vitro cell culture studies showed that the hormonal form of vitamin D3, 1α, 25-dihydroxyvitamin D3, significantly (p < 0.05) affects the human epigenome at thousands of genomic loci. Phase II of the VitDbol vitamin D intervention trial (NCT02063334) involved a proof-of-principle study of one individual, who was exposed three times every 28 days to an oral bolus (2000 μg) of vitamin D3 . Blood samples were taken directly before each supplementation as well as one and two days after, chromatin was isolated from peripheral blood mononuclear cells without any further in vitro culture and at all nine time points epigenome-wide chromatin accessibility was assessed by applying FAIRE-seq (formaldehyde-assisted isolation of regulatory elements sequencing). The vitamin D3 bolus resulted in an average raise in 25-hydroxyvitamin D3 (25(OH)D3 ) serum concentration of 11.9 and 19.4 nM within one and two days, respectively. Consistently accessible chromatin was detected at 5205 genomic loci, the 853 most prominent of which a self-organizing map algorithm classified into early, delayed and non-responding genomic regions: 70 loci showed already after one day and 361 sites after two days significant (p < 0.0001) chromatin opening or closing. Interestingly, more than half of these genomic regions overlap with transcription start sites, but the change of chromatin accessibility at these sites has no direct effect on the transcriptome. Some of the vitamin D responsive chromatin sites cluster at specific loci within the human genome, the most prominent of which is the human leukocyte antigen region in chromosome 6. In conclusion, this study demonstrates that under in vivo conditions a rather minor rise in 25(OH)D3 serum levels is sufficient to result in significant changes at hundreds of sites within the epigenome of human leukocytes.