title: VDR primary targets by genome-wide transcriptional profiling.
abstract: There is growing evidence that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) plays a role in breast cancer prevention and survival. It elicits a variety of antitumor activities like controlling cellular differentiation, proliferation and angiogenesis. Most of its biological effects are exerted via its nuclear receptor which acts as a transcriptional regulator. Here, we carried out a genome-wide investigation of the primary transcriptional targets of 1α,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1α,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1α,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1α,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1α,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1α,25(OH)2D3 treatment provides a resource of primary 1α,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells.
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: frauke.goeman@gmail.com.
authors.forename: Frauke
authors.initials: F
authors.lastname: Goeman
authors.affiliation: Laboratory of Epigenetic, Molecular Medicine Area, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: denicola@ifo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nicola
authors.affiliation: HPC CINECA, 00185 Rome, Italy. Electronic address: p.donoriodemeo@cineca.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: D'Onorio De Meo
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: matteo.pallocca@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pallocca
authors.affiliation: Laboratory of Epigenetic, Molecular Medicine Area, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: beradiel87@gmail.com.
authors.forename: Berardino
authors.initials: B
authors.lastname: Elmi
authors.affiliation: HPC CINECA, 00185 Rome, Italy. Electronic address: t.castrignano@cineca.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Castrignanò
authors.affiliation: Institute of Biomembranes and Bioenergetics of the National Research Council and Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, Italy. Electronic address: graziano.pesole@biologia.uniba.it.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.affiliation: Molecular Chemoprevention Unit, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: strano@ifo.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: gblandino@activep53.eu.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.affiliation: Laboratory of Epigenetic, Molecular Medicine Area, Italian National Cancer Institute "Regina Elena", 00144 Rome, Italy. Electronic address: fanciulli@ifo.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fanciulli
authors.affiliation: Department of Oncology, McMaster University, Main Street West Hamilton, ON L8S 4K1, Canada. Electronic address: muti@mcmaster.ca.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: 1α,25-Dihydroxyvitamin D3; ChIP-Seq; Genome-wide transcriptional profiling; H3K4me3; Mutant p53; RNA-Seq; Vitamin D receptor