دورية أكاديمية
p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response
| العنوان: | p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response |
|---|---|
| المؤلفون: | Serra, François, Nieto-Aliseda, Andrea, Fanlo-Escudero, Lucía, Rovirosa, Llorenç, Cabrera-Pasadas, Mónica, Lazarenkov, Aleksey, Urmeneta, Blanca, Alcalde-Merino, Alvaro, Nola, Emanuele M, Okorokov, Andrei L, Fraser, Peter, Graupera, Mariona, Castillo, Sandra D, Sardina, Jose L, Valencia, Alfonso, Javierre, Biola M |
| المصدر: | Nature Communications , 15 , Article 2821. (2024) |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | Activation of the p53 tumor suppressor triggers a transcriptional program to control cellular response to stress. However, the molecular mechanisms by which p53 controls gene transcription are not completely understood. Here, we uncover the critical role of spatio-temporal genome architecture in this process. We demonstrate that p53 drives direct and indirect changes in genome compartments, topologically associating domains, and DNA loops prior to one hour of its activation, which escort the p53 transcriptional program. Focusing on p53-bound enhancers, we report 340 genes directly regulated by p53 over a median distance of 116 kb, with 74% of these genes not previously identified. Finally, we showcase that p53 controls transcription of distal genes through newly formed and pre-existing enhancer-promoter loops in a cohesin dependent manner. Collectively, our findings demonstrate a previously unappreciated architectural role of p53 as regulator at distinct topological layers and provide a reliable set of new p53 direct target genes that may help designs of cancer therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10190047/1/s41467-024-46666-1.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10190047Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10190047/1/s41467-024-46666-1.pdfTest https://discovery.ucl.ac.uk/id/eprint/10190047Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.629956D8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |