p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response

• DOI: 10.1038/s41467-024-46666-1
• Publication Date: 2024-04-01T16:01:52Z
• Authors: François Serra; Andrea Nieto-Aliseda; Lucía Fanlo-Escudero; Llorenç Rovirosa; Mónica Cabrera-Pa...; Aleksey Lazarenkov; Blanca Urmeneta; Alvaro Alcalde-Me...; Emanuele M. Nola; Andrei L. Okorokov; Peter Fraser; Mariona Graupera; Sandra D. Castillo; Jose L. Sardina; Alfonso Valencia; Biola M. Javierre
• Keywords: Transcription

Abstract Activation of the p53 tumor suppressor triggers a transcriptional program to control cellular response stress. However, molecular mechanisms by which controls gene transcription are not completely understood. Here, we uncover critical role spatio-temporal genome architecture in this process. We demonstrate that drives direct and indirect changes compartments, topologically associating domains, DNA loops prior one hour its activation, escort program. Focusing on p53-bound enhancers, report 340 genes directly regulated over median distance 116 kb, with 74% these previously identified. Finally, showcase distal through newly formed pre-existing enhancer-promoter cohesin dependent manner. Collectively, our findings unappreciated architectural as regulator at distinct topological layers provide reliable set new target may help designs cancer therapies.