FRI164 The Glucocorticoid Receptor is Required for Efficient Aldosterone-induced Transcription by the Mineralocorticoid Receptor

Abstract Disclosure: T.A. Johnson: None. G. Fettweis: None. K. Wagh: None. B. Almeida-Prieto: None. G.L. Hager: None. D. Alvarez de la Rosa: None. The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There is evidence in the literature that the two receptors interact both functionally and physically, but the global role of this interdependence is poorly understood (1,2). Here, we analyze the impact of GR co-expression on MR genome-wide chromatin binding and transcriptional responses to aldosterone and glucocorticoids. Our data show that GR co-expression alters MR genome-wide binding in locus- and ligand-specific ways. MR binding to consensus hormone response elements is affected by GR. Additionally, gene responses by MR in the absence of GR are weak and show poor correlation with chromatin binding. In contrast, co-expression of GR greatly potentiates genome-wide MR-mediated transcription, particularly in response to aldosterone. These aldosterone-mediated transcriptional responses do not occur with GR alone. Finally, single molecule tracking of MR in live cells indicates that the presence of GR contributes to productive chromatin binding events. Together, our data indicate that co-expression of GR enables optimal aldosterone-mediated MR transcriptional activity, even in the absence of glucocorticoids. REFERENCES: (1) Mayumi Nishi et al., J Neuroscience. 2004 May 26; 24(21):4918 - 4927. (2) Liu et al., PNAS. Dec 1995; 92: 12480-12484. Presentation Date: Friday, June 16, 2023