학술논문
p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response.
Document Type
Academic Journal
Author
Serra F; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Nieto-Aliseda A; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Fanlo-Escudero L; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Rovirosa L; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Cabrera-Pasadas M; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Barcelona Supercomputing Center, Barcelona, Spain.; Lazarenkov A; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Urmeneta B; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Alcalde-Merino A; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Nola EM; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Okorokov AL; Wolfson Institute for Biomedical Research, University College London, London, UK.; Fraser P; Department of Biological Science, Florida State University, Tallahassee, FL, USA.; Graupera M; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.; Castillo SD; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Sardina JL; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Valencia A; Barcelona Supercomputing Center, Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.; Javierre BM; Josep Carreras Leukaemia Research Institute, Barcelona, Spain. bmjavierre@carrerasresearch.org.; Institute for Health Science Research Germans Trias i Pujol, Barcelona, Spain. bmjavierre@carrerasresearch.org.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2024. The Author(s).)
(© 2024. The Author(s).)