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| Status |
Public on Apr 17, 2024 |
| Title |
p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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, using a multi-omics integration framework, 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 within minutes of its activation, which escort the p53 transcriptional program along time. Focused on p53-bound enhancers, we report a core transcriptional program of 340 genes directly regulated by p53 over distance, most of these 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. Taken together, 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 future designs of p53-based cancer therapies.
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| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K27ac and H3K4me1 in HCT116 cells.
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| Contributor(s) |
Serra F, Nieto-Aliseda A, Rovirosa L, Cabrera-Pasadas M, Fanlo L, Lazarenkov A, Urmeneta B, Okorokov AL, Fraser P, Sardina JL, Valencia A, Javierre BM |
| Citation(s) |
38561401 |
| |
| Submission date |
Jul 03, 2023 |
| Last update date |
Apr 18, 2024 |
| Contact name |
Biola M Javierre |
| E-mail(s) |
bmjavierre@carrerasresearch.org
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| Organization name |
Josep Carreras Leukaemia Research Institute
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| Lab |
3D Chromatin Organization
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| Street address |
Ctra de Can Ruti, Camà de les Escoles , s/n
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| City |
Badalona |
| State/province |
Barcelona |
| ZIP/Postal code |
08916 |
| Country |
Spain |
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| Platforms (1) |
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| Samples (26)
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| This SubSeries is part of SuperSeries: |
| GSE235947 |
p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response |
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| Relations |
| BioProject |
PRJNA990719 |
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