title: Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.
abstract: ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses.
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: cagri.gulec@gmail.com.
authors.forename: Cagri
authors.initials: C
authors.lastname: Gulec
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: neslic@istanbul.edu.tr.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Coban
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: ozsaitb@istanbul.edu.tr.
authors.forename: Bilge
authors.initials: B
authors.lastname: Ozsait-Selcuk
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: semasirma@gmail.com.
authors.forename: Sema
authors.initials: S
authors.lastname: Sirma-Ekmekci
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: ozlm-yildirim@hotmail.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Yildirim
authors.affiliation: Istanbul University, Institute for Experimental Medicine, Department of Genetics, Vakif Gureba C. Capa-Fatih, 34104 Istanbul, Turkey. Electronic address: nihanerginel@yahoo.com.
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000502:physiology*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013844:Thiazoles / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000494:pharmacology; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; C506895:SPP1 protein, human; D013844:Thiazoles; D013882:Thiosemicarbazones; D053495:Osteopontin; C092451:CGP 52608
keywords: Atherosclerosis; ChIP-on-chip; Nuclear receptors; Target genes