Glucocorticoid receptor tethered mineralocorticoid receptors increase glucocorticoid-induced transcriptional responses

Mineralocorticoid and glucocorticoid receptors (MRs and GRs) constitute a functionally important dual receptor system detecting and transmitting circulating corticosteroid signals. High expression of MRs and GRs occurs in the same cells in the limbic system, the primary site of glucocorticoid action on cognition, behaviour and mood, however modes of interaction between the receptors are poorly characterised. We used ChIP-nexus for high-resolution genome-wide characterisation of MR and GR DNA binding profiles in neuroblastoma cells and demonstrate recruitment to highly similar DNA binding sites. Expressed MR or GR showed differential regulation of endogenous gene targets, including Syt2 and Ddc, while co-expression produced augmented transciptional responses even when MRs (MR-XDBD) were unable to bind DNA. ChIP confirmed MR-XDBD could be tethered to chromatin by GR. Our data demonstrate MR can interact at individual genomic DNA sites in multiple modes and suggest a role for MR in increasing the dynamic response to glucocorticoids.

Creator(s) Stafford Lightman, Becky Conway-Campbell, Caroline Rivers, John Pooley, Mark Rogers
Publication date 07 Dec 2018
Language eng
Publisher University of Bristol
Licence Non-Commercial Government License for public sector information
DOI 10.5523/bris.28jhb462ss43d2ujuwwnwl30lb
Complete download (zip) https://data.bris.ac.uk/datasets/28jhb462ss43d2ujuwwnwl30lb/28jhb462ss43d2ujuwwnwl30lb.zip
Citation Stafford Lightman, Becky Conway-Campbell, Caroline Rivers, John Pooley, Mark Rogers (2018): Glucocorticoid receptor tethered mineralocorticoid receptors increase glucocorticoid-induced transcriptional responses. https://doi.org/10.5523/bris.28jhb462ss43d2ujuwwnwl30lb
Total size 1.6 MiB

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