期刊
PLOS ONE
卷 15, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0227520
关键词
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资金
- Biotechnology and Biological Sciences Research Council [BB/L007622/1]
- Intramural Research Program of the NIH, National Cancer Institute
- Center for Cancer Research (USA)
- Neuroendocrinology Charitable Trust [12/13-5751, 13/14-5810]
- Society for Endocrinology Early Career Grant
- Biotechnology and Biological Sciences Research Council International Scientific Interchange Scheme
- British Society for Neuroendocrinology Project Support Grant
- BBSRC Alert 13 capital grant [BB/L014181/1]
- BBSRC [BB/L007622/1, BB/L014181/1] Funding Source: UKRI
- MRC [MR/R010919/1] Funding Source: UKRI
- NATIONAL CANCER INSTITUTE [ZICBC011574] Funding Source: NIH RePORTER
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.
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