Other Open Access
AP-1 Imprints a Reversible Transcriptional Programme of Senescent Cells
Ricardo Iván Martínez-Zamudio;
Pierre-François Roux;
José Américo N L F de Freitas;
Lucas Robinson;
Gregory Doré;
Utz Herbig;
Oliver Bischof;
Jesus Gil;
Bin Sun;
Clemens A. Schmitt;
Maja Milanovic;
Dimitri Belenki
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.
| Name | Size | |
|---|---|---|
|
CIRCOS.zip
md5:db5bf1b8f43941f8ea8216d2f3052b55 |
34.6 MB | Download |
|
Interactive_TF_lexicon_heatmap.html
md5:8ad649c407ea61119a537f5bb2760d26 |
6.8 MB | Download |
|
NETWORKS.zip
md5:7ffe9e5e9803c61d2d3b62a0e5c1a0ef |
7.3 MB | Download |
|
TABLE_S1.xlsx
md5:ff157ecf9c1c491874d73685a9c73679 |
17.5 MB | Download |
|
TABLE_S10.xlsx
md5:f5f4397d1198c4fb087f5e272b5eb981 |
91.5 kB | Download |
|
TABLE_S2.xlsx
md5:e071578b7011dec9cbd77823d14c9e44 |
35.5 MB | Download |
|
TABLE_S3.xlsx
md5:01d55cbf927711bd71a24a311d0f8f0c |
486.8 kB | Download |
|
TABLE_S4.xlsx
md5:d90b15109850789126a5a27dbe974efc |
100.9 kB | Download |
|
TABLE_S5.xlsx
md5:1ea7a8b8c4ba46ac318e5a2355d5a767 |
3.6 MB | Download |
|
TABLE_S6.xlsx
md5:0e6d7bf447fd1501a1b9dd53aef2e33a |
43.2 MB | Download |
|
TABLE_S7.xlsx
md5:3f5fee154b7be55da2a9244016d3e074 |
13.0 kB | Download |
|
TABLE_S8.xlsx
md5:075d4b8d7d6ecdfa1a653d7701a87e50 |
11.1 kB | Download |
|
TABLE_S9.xlsx
md5:222ab09ba026dc9316e0c4f7c761d421 |
29.8 kB | Download |
|
WORKFLOW.tar.gz
md5:acb176145a0bd9243b46bbf4144dc913 |
58.4 GB | Download |
| All versions | This version | |
|---|---|---|
| Views | 813 | 556 |
| Downloads | 3,836 | 2,435 |
| Data volume | 197.3 TB | 118.7 TB |
| Unique views | 717 | 494 |
| Unique downloads | 882 | 668 |
- Publication date:
- March 27, 2020
- DOI:
-
- Keyword(s):
- Cellular senescence, cell fate transition, epigenome dynamics, transcriptome dynamics, transcription factor network, enhancer, epigenetic bookmarking, multidimensional profiling
- Published in:
- Nature Cell Biology:.
- Related identifiers:
- Cited by
- 10.1038/s41556-020-0529-5 (Journal article)
- License (for files):
- Creative Commons Attribution 4.0 International