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:
https://doi.org/10.1371/journal.pone.0227520
Souhrn
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
Zdroje
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