The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There are indications that both receptors interact functionally and physically, but the precise role of this interdependence is poorly understood. Here, we analyzed the impact of GR coexpression on MR genome-wide transcriptional responses and chromatin binding upon activation by aldosterone and glucocorticoids, both physiological ligands of this receptor. Transcriptional responses of MR in the absence of GR result in fewer regulated genes. In contrast, coexpression of GR potentiates MR-mediated transcription, particularly in response to aldosterone, both in cell lines and in the more physiologically relevant model of mouse colon organoids. MR chromatin binding is altered by GR coexpression in a locus- and ligand-specific way. Single-molecule tracking of MR suggests that the presence of GR contributes to productive binding of MR/aldosterone complexes to chromatin. Together, our data indicate that coexpression of GR potentiates aldosterone-mediated MR transcriptional activity, even in the absence of glucocorticoids.

中文翻译：

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糖皮质激素受体增强盐皮质激素受体诱导的醛固酮转录


糖皮质激素和盐皮质激素受体 （分别为 GR 和 MR） 具有不同但重叠的生理和病理生理功能。有迹象表明，这两种受体在功能和物理上相互作用，但这种相互依赖的确切作用知之甚少。在这里，我们分析了 GR 共表达对醛固酮和糖皮质激素激活后 MR 全基因组转录反应和染色质结合的影响，醛固酮和糖皮质激素都是该受体的生理配体。在没有 GR 的情况下，MR 的转录反应导致调节基因减少。相比之下，GR 的共表达增强了 MR 介导的转录，特别是在细胞系和更生理相关的小鼠结肠类器官模型中对醛固酮的反应。MR 染色质结合通过 GR 共表达以基因座和配体特异性方式发生改变。MR 的单分子追踪表明，GR 的存在有助于 MR/醛固酮复合物与染色质的有效结合。总之，我们的数据表明，即使在没有糖皮质激素的情况下，GR 的共表达也能增强醛固酮介导的 MR 转录活性。