Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA.

John Pooley, Caroline A Rivers, Michael Kilcooley, Susana N Paul, Ayse Derya Cavga, Yvonne M Kershaw, Serena Muratcioglu, Attila Gursoy, Ozlem Keskin, Stafford L Lightman

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Glucocorticoid (GR) and mineralocorticoid receptors (MR) are believed to classically bind DNA as homodimers or MR-GR heterodimers to influence gene regulation in response to pulsatile basal or stress-evoked glucocorticoid secretion. Pulsed corticosterone presentation reveals MR and GR co-occupy DNA only at the peaks of glucocorticoid oscillations, allowing interaction. GR DNA occupancy was pulsatile, while MR DNA occupancy was prolonged through the inter-pulse interval. In mouse mammary 3617 cells MR-GR interacted in the nucleus and at a chromatin-associated DNA binding site. Interactions occurred irrespective of ligand type and receptors formed complexes of higher order than heterodimers. We also detected MR-GR interactions ex-vivo in rat hippocampus. An expanded range of MR-GR interactions predicts structural allostery allowing a variety of transcriptional outcomes and is applicable to the multiple tissue types that co-express both receptors in the same cells whether activated by the same or different hormones.
Original languageEnglish
Article numbere0227520
Number of pages35
JournalPLoS ONE
Volume15
Issue number1
DOIs
Publication statusPublished - 10 Jan 2020

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