Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA
| Autor: | Ozlem Keskin, Serena Muratcioglu, Michael Kilcooley, John R. Pooley, Ayse Derya Cavga, Attila Gursoy, Caroline A Rivers, Susana N. Paul, Stafford L. Lightman, YM Kershaw |
|---|---|
| Přispěvatelé: | Cavga, Ayşe Derya, Gürsoy, Attila (ORCID 0000-0002-2297-2113 & YÖK ID 8745), Keskin Özkaya, Zehra Özlem (ORCID 0000-0002-4202-4049 & YÖK ID 26605), Pooley, John R., Rivers, Caroline A., Kilcooley, Michael T., Paul, Susana N., Kershaw, Yvonne M., Muratçıoğlu, Serena, Lightman, Stafford L., Graduate School of Sciences and Engineering, College of Engineering, Department of Chemical and Biological Engineering |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Hippocampus Biochemistry Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Glucocorticoid receptor Medicine and Health Sciences Lipid Hormones Receptor Materials Aldosterone Multidisciplinary Chemistry Ultradian Rhythm Brain Ligand (biochemistry) Chromatin Precipitation Techniques Cell biology Optical Equipment Physical Sciences Engineering and Technology Medicine Anatomy Dimerization Glucocorticoid Research Article medicine.drug Science Materials Science Equipment Research and Analysis Methods Multidisciplinary sciences Cell Line 03 medical and health sciences Receptors Glucocorticoid Allosteric Regulation DNA-binding proteins medicine Animals Immunoprecipitation Protein Interaction Domains and Motifs Amino Acid Sequence Binding site Protein Structure Quaternary Protein Interactions Dimers Cell Nucleus DNA Heterodimer Mineralocorticoid receptor Corticosterone Binding Sites Biology and Life Sciences Proteins Prisms Polymer Chemistry Co-Immunoprecipitation Hormones Rats DNA binding site Receptors Mineralocorticoid 030104 developmental biology Glucocorticoid secretion Oligomers Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE, Vol 15, Iss 1, p e0227520 (2020) Pooley, J, Rivers, C A, Kilcooley, M, Paul, S N, Cavga, A D, Kershaw, Y M, Muratcioglu, S, Gursoy, A, Keskin, O & Lightman, S L 2020, ' Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA. ', PLoS ONE, vol. 15, no. 1, e0227520 . https://doi.org/10.1371/journal.pone.0227520 PLOS One PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0227520 |
| Popis: | 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. Biotechnology and Biological Sciences Research Council (BBSRC); Neuroendocrinology Charitable Trust; BBSRC Alert 13 Capital Grant; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research (USA); Society for Endocrinology Early Career Grant; Biotechnology and Biological Sciences Research Council International Scientific Interchange Scheme Award; British Society for Neuroendocrinology Project Support Grant |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|