Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway

• Published in: International journal of immunopathology and pharmacology 2020, Vol.34, p.2058738420946192-2058738420946192
• Main Authors: Chung, Young Sun, Jin, Hong Lan, Jeong, Kwang Won
• Format: Article
• Language: English
• Subjects: A549 Cells; Cell lines; Dexamethasone - pharmacology; Epithelial Sodium Channels - genetics; Epithelial Sodium Channels - metabolism; Gene expression; Gene Expression Regulation, Neoplastic; Glucocorticoids; Glucocorticoids - pharmacology; Hepatocyte Nuclear Factor 3-alpha - genetics; Hepatocyte Nuclear Factor 3-alpha - metabolism; Humans; Kinases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Molecular modelling; Nuclear receptors; Original; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - metabolism; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; Ribonucleic acid; RNA; Signal Transduction; Tacrolimus; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism; Tacrolimus-binding protein; Transcription factors
• ISSN: 2058-7384; 0394-6320; 2058-7384
• DOI: 10.1177/2058738420946192

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.