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HERO ID
3854369
Reference Type
Journal Article
Title
Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines
Author(s)
Gulec, C; Coban, N; Ozsait-Selcuk, B; Sirma-Ekmekci, S; Yildirim, O; Erginel-Unaltuna, N
Year
2017
Is Peer Reviewed?
Yes
Journal
Experimental Cell Research
ISSN:
0014-4827
EISSN:
1090-2422
Volume
353
Issue
1
Page Numbers
6-15
Language
English
PMID
28238834
DOI
10.1016/j.yexcr.2017.02.028
Web of Science Id
WOS:000398756700002
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.
Tags
IRIS
•
Arsenic Hazard ID
Lit Search Updates Oct 2015 to Jan 2019
PubMed
WOS
2.5 Update 2015-2019: Title & Abstract Screening
Not relevant to PECO
•
Chloroprene
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