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.

中文翻译：

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FOXA1 在糖皮质激素受体通路中对 ENACα 基因的细胞特异性表达。

介绍：

糖皮质激素受体（GR）是研究最广泛的配体依赖性核受体之一。表达 GR 靶向的单个基因所需的转录调节因子的组合因细胞类型而异；然而，这种细胞类型特异性基因表达调控的机制尚不清楚。

方法：

在这里，我们研究了两种不同细胞系 A549 和 ARPE-19 中 GR 调控的基因，并使用 RNA-seq 和 RT-qPCR 检查了基因表达如何根据先驱因子的影响而变化。

结果：

我们的 RNA-seq 结果确定了 19 个和 63 个由 GR 调节的基因，它们分别是 ARPE-19 特异性和 A549 特异性，这表明 GR 以细胞类型特异性方式诱导不同基因组的表达。RT-qPCR 证实上皮钠通道 ( ENACα ) 基因是 ARPE-19 细胞特异性 GR 靶基因，而 FK506 结合蛋白 5 ( FKBP5 ) 基因是 A549 细胞特异性。在 FOXA1 缺陷型 ARPE-19 细胞中ENACα表达显着降低，这表明 FOXA1 可能作为先驱因子发挥作用，使ENACα在 ARPE-19 细胞中而非 A549 细胞中选择性表达。

结论：

这些发现表明ARPE-19 细胞中ENACα的表达受 FOXA1 的调节，并提供了对 GR 调节基因的细胞类型特异性表达的分子机制的见解。