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

Autoři: John R. Pooley aff001;  Caroline A. Rivers aff001;  Michael T. Kilcooley aff001;  Susana N. Paul aff001;  Ayse Derya Cavga aff003;  Yvonne M. Kershaw aff001;  Serena Muratcioglu aff004;  Attila Gursoy aff003;  Ozlem Keskin aff003;  Stafford L. Lightman aff001
Působiště autorů: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom aff001;  Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America aff002;  Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey aff003;  Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America aff004;  Howard Hughes Medical Institute, University of California, Berkeley, California, United States of America aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227520


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.

Klíčová slova:

Aldosterone – Co-immunoprecipitation – Dimers – DNA-binding proteins – Hippocampus – Hormones – Prisms – Protein interactions


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