title: The vitamin D-dependent transcriptome of human monocytes.
abstract: Monocytes are important cells of the innate immune system that can differentiate into macrophages and dendritic cells. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), serves as a ligand of the nuclear receptor vitamin D receptor (VDR). A key physiological function of 1,25(OH)2D3is the defense against pathogens, such as those causing tuberculosis, that involves the modulation of the monocyte transcriptome. THP-1 cells are an established model of human monocytes, for which the at present largest set of 1,25(OH)2D3-affected genome-wide data are available. Here we summarize the insight obtained from the recent transcriptome of 1,25(OH)2D3-stimulated THP-1 cells, that was determined by triplicate RNA sequencing (RNA-seq). Primary and secondary vitamin D target genes being up- and down-regulated were related to changes in the epigenome of THP-1 cells, such as 1,25(OH)2D3-dependent chromatin opening and modulation of the genome-wide association of the transcription factors VDR and CCCTC-binding factor (CTCF) with their respective genomic binding sites. The anti-microbial response is the top-ranking early physiological function represented by 1,25(OH)2D3-stimulated genomic regions and genes, but also other immunity-related pathways, such as IL10 signaling, are activated. Taken together, the epigenomic and transcriptomic responses of THP-1 cells to 1,25(OH)2D3represent a master example of the impact of vitamin D on human physiology.
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Neme
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Veijo
authors.initials: V
authors.lastname: Nurminen
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Seuter
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland. Electronic address: carsten.carlberg@uef.fi.
authors.forename: Carsten
authors.initials: C
authors.lastname: Carlberg
mesh_terms: D000076246:CCCTC-Binding Factor; D002117:Calcitriol / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; D014157:Transcription Factors; D002117:Calcitriol
keywords: Epigenome; Monocytes; RNA-seq; Transcriptome; VDR; Vitamin D