دورية أكاديمية
The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation.
| العنوان: | The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation. |
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| المؤلفون: | Rinaldi, Lorenzo, Fettweis, Grégory, Kim, Sohyoung, Garcia, David A, Fujiwara, Saori, Johnson, Thomas A, Tettey, Theophilus T, Ozbun, Laurent, Pegoraro, Gianluca, Puglia, Michele, Blagoev, Blagoy, Upadhyaya, Arpita, Stavreva, Diana A, Hager, Gordon L |
| المصدر: | Science Advances, 8 (13), eabj8360 (2022-04) |
| بيانات النشر: | American Association for the Advancement of Science, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Chromosomal Proteins, Non-Histone, NIPBL protein, human, Receptors, Glucocorticoid, cohesins, Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, Gene Expression Regulation, Humans, Chromosomal Proteins, Non-Histone/genetics, Chromosomal Proteins, Non-Histone/metabolism, Receptors, Glucocorticoid/genetics, Acute myeloid leukemia, Gene activities, Gene-regulation, Genome mapping, Glucocorticoid receptor, Real- time, Single molecule experiments, Single-molecule tracking, Multidisciplinary, Life sciences, Biochemistry, biophysics & molecular biology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire |
| الوصف: | The cohesin complex is central to chromatin looping, but mechanisms by which these long-range chromatin interactions are formed and persist remain unclear. We demonstrate that interactions between a transcription factor (TF) and the cohesin loader NIPBL regulate enhancer-dependent gene activity. Using mass spectrometry, genome mapping, and single-molecule tracking methods, we demonstrate that the glucocorticoid (GC) receptor (GR) interacts with NIPBL and the cohesin complex at the chromatin level, promoting loop extrusion and long-range gene regulation. Real-time single-molecule experiments show that loss of cohesin markedly diminishes the concentration of TF molecules at specific nuclear confinement sites, increasing TF local concentration and promoting gene regulation. Last, patient-derived acute myeloid leukemia cells harboring cohesin mutations exhibit a reduced response to GCs, suggesting that the GR-NIPBL-cohesin interaction is defective in these patients, resulting in poor response to GC treatment. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501Test article peer reviewed |
| اللغة: | English |
| العلاقة: | urn:issn:2375-2548 |
| DOI: | 10.1126/sciadv.abj8360 |
| الوصول الحر: | https://orbi.uliege.be/handle/2268/303028Test |
| حقوق: | restricted access http://purl.org/coar/access_right/c_16ecTest info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsorb.303028 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1126/sciadv.abj8360 |
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