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ABSTRACT: Introduction
The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type-specific regulation of gene expression are not yet clear.Methods
Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how gene expression varied according to the effect of pioneer factors using RNA-seq and RT-qPCR.Results
Our RNA-seq results identified 19 and 63 genes regulated by GR that are ARPE-19-specific and A549-specific, respectively, suggesting that GR induces the expression of different sets of genes in a cell type-specific manner. RT-qPCR confirmed that the epithelial sodium channel (ENACα) gene is an ARPE-19 cell-specific GR target gene, whereas the FK506 binding protein 5 (FKBP5) gene was A549 cell-specific. There was a significant decrease in ENACα expression in FOXA1-deficient ARPE-19 cells, suggesting that FOXA1 might function as a pioneer factor enabling the selective expression of ENACα in ARPE-19 cells but not in A549 cells.Conclusion
These findings indicate that ENACα expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type-specific expression of GR-regulated genes.
SUBMITTER: Chung YS
PROVIDER: S-EPMC7450284 | biostudies-literature | 2020 Jan-Dec
REPOSITORIES: biostudies-literature
Chung Young Sun YS Jin Hong Lan HL Jeong Kwang Won KW
International journal of immunopathology and pharmacology 20200101
<h4>Introduction</h4>The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type-specific regulation of gene expression are not yet clear.<h4>Methods</h4>Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how ge ...[more]