Skip to content

Glucocorticoid Receptor-Tethered Mineralocorticoid Receptors Increase Glucocorticoid-Induced Transcriptional Responses

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1044-1056
Number of pages13
JournalEndocrinology
Volume160
Issue number5
Early online date11 Mar 2019
DOIs
DateAccepted/In press - 1 Mar 2019
DateE-pub ahead of print - 11 Mar 2019
DatePublished (current) - 1 May 2019

Abstract

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, behavior, and mood; however, modes of interaction between the receptors are poorly characterized. We used chromatin immunoprecipitation with nucleotide resolution using exonuclease digestion, unique barcode, and single ligation (ChIP-nexus) for high-resolution genome-wide characterization 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, whereas coexpression produced augmented transcriptional responses even when MRs were unable to bind DNA (MR-XDBD). ChIP confirmed that MR-XDBD could be tethered to chromatin by GR. Our data demonstrate that MR can interact at individual genomic DNA sites in multiple modes and suggest a role for MR in increasing the transcriptional response to glucocorticoids.

Additional information

Copyright © 2019 Endocrine Society.

Download statistics

No data available

Documents

Documents

  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via OUP at https://doi.org/10.1210/en.2018-00819 . Please refer to any applicable terms of use of the publisher.

    Final published version, 1 MB, PDF document

    Licence: CC BY

DOI

View research connections

Related faculties, schools or groups