Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway
- Authors
- Chung, Y.S.; Jin, H.L.; Jeong, K.W.
- Issue Date
- Aug-2020
- Publisher
- SAGE PUBLICATIONS INC
- Keywords
- ENACα; FOXA1; glucocorticoid receptor; pioneer factor
- Citation
- International journal of immunopathology and pharmacology, v.34
- Journal Title
- International journal of immunopathology and pharmacology
- Volume
- 34
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/78222
- DOI
- 10.1177/2058738420946192
- ISSN
- 0394-6320
- 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.
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