title: In vitro exposure of human blood mononuclear cells to active vitamin D does not induce substantial change to DNA methylation on a genome-scale.
abstract: It is well-established that vitamin D impacts gene regulation via vitamin D response elements (VDREs) across the genome. Recent evidence, primarily at a locus-specific level, suggests that alterations to DNA methylation may also be a relevant mechanism through which vitamin D regulates gene expression. Given the intense interest in vitamin D, particularly as an immune modifier, we sought to examine the impact of vitamin D exposure on the immune cell methylome in vitro. We exposed primary human blood mononuclear cells with up to 100nM calcitriol for up to 120h, and measured genome-scale DNA methylation response using the Illumina Infinium HumanMethylation450 beadchip array. We observed that, while the expression of known vitamin D responsive genes was clearly altered by calcitriol exposure, substantial genome-scale changes to DNA methylation were not induced. Our data suggests that, over the exposure period measured, changes to DNA methylation may not be a predominant mechanism through which vitamin D impacts gene expression in human immune cells.
authors: Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Victoria 3010, Australia. Electronic address: raul.chavez@mcri.edu.au.
authors: Raul A
authors: RA
authors: Chavez Valencia
authors: Department of Paediatrics, The University of Melbourne, Victoria 3010, Australia; Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia. Electronic address: david.martino@mcri.edu.au.
authors: David J
authors: DJ
authors: Martino
authors: Department of Paediatrics, The University of Melbourne, Victoria 3010, Australia; Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia. Electronic address: richard.saffery@mcri.edu.au.
authors: Richard
authors: R
authors: Saffery
authors: Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Victoria 3010, Australia. Electronic address: justine.ellis@mcri.edu.au.
authors: Justine A
authors: JA
authors: Ellis
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000502:physiology*; D002478:Cells, Cultured; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004790:Enzyme Induction; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: C000717967:DNMT3A protein, human; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D002117:Calcitriol
keywords: 1,25-Dihydroxyvitamin D(3); DNA methylation; Epigenetics; Infinium; Mononuclear cells; Vitamin D