3731264
doi
10.5281/zenodo.3731264
oai:zenodo.org:3731264
Pierre-François Roux
Johnson & Johnson, Upstream Skin Research, 92130 Issy-les-Moulineaux, France
José Américo N L F de Freitas
Institut Pasteur, INSERM U.993
Lucas Robinson
Institut Pasteur, INSERM U993
Gregory Doré
Institut Pasteur, INSERM U993
Utz Herbig
Rutgers Biomedical & Health Sciences, Rutgers University
Oliver Bischof
Institut Pasteur, INSERM U993
Jesus Gil
MRC London Institute of Medical Sciences (LMS), Du Cane Road, London, W12 0NN, UK
Bin Sun
MRC London Institute of Medical Sciences (LMS), Du Cane Road, London, W12 0NN, UK
Clemens A. Schmitt
Kepler University Hospital, Department of Hematology and Oncology, Johannes Kepler University, Krankenhausstraße 9, 4020 Linz, Austria
Maja Milanovic
Charité - University Medical Center, Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, Augustenburger Platz 1, 13353 Berlin, Germany
Dimitri Belenki
Charité - University Medical Center, Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, Augustenburger Platz 1, 13353 Berlin, Germany
AP-1 Imprints a Reversible Transcriptional Programme of Senescent Cells
Ricardo Iván Martínez-Zamudio
Rutgers Biomedical & Health Sciences, Rutgers University
doi:10.1038/s41556-020-0529-5
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
Cellular senescence, cell fate transition, epigenome dynamics, transcriptome dynamics, transcription factor network, enhancer, epigenetic bookmarking, multidimensional profiling
<p>Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.</p>
Zenodo
2020-03-27
info:eu-repo/semantics/other
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public
10.1038/s41556-020-0529-5
Is cited by
doi
10.5281/zenodo.1493871
isVersionOf
doi
Nature Cell Biology
2020-03-27