J. Campisi, Aging, cellular senescence, and cancer, Annu. Rev. Physiol, vol.75, pp.685-705, 2013.

M. Collado and M. Serrano, Senescence in tumours: evidence from mice and humans, Nat. Rev. Cancer, vol.10, pp.51-57, 2010.

J. I. Jun and L. F. Lau, The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing, Nat. Cell Biol, vol.12, pp.676-685, 2010.

M. Demaria, An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA, Dev. Cell, vol.31, pp.722-733, 2014.

A. Sagiv and V. Krizhanovsky, Immunosurveillance of senescent cells: The bright side of the senescence program, Biogerontology, vol.14, pp.617-628, 2013.

J. M. Van-deursen, The role of senescent cells in ageing, Nature, vol.509, pp.439-446, 2014.

T. S. Rai and P. D. Adams, Lessons from senescence: Chromatin maintenance in non-proliferating cells, Biochim. Biophys. Acta, vol.1819, pp.322-331, 2012.

R. Salama, M. Sadaie, M. Hoare, and M. Narita, Cellular senescence and its effector programs, Genes Dev, vol.28, pp.99-114, 2014.

W. F. Marzluff, E. J. Wagner, and R. J. Duronio, Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail, Nat. Rev. Genet, vol.9, pp.843-854, 2008.

P. B. Talbert and S. Henikoff, Histone variants-ancient wrap artists of the epigenome, Nat. Rev. Mol. Cell Biol, vol.11, pp.264-275, 2010.

I. Maze, K. Noh, A. Soshnev, and C. D. Allis, Every amino acid matters: essential contributions of histone variants to mammalian development and disease, Nat. Rev. Genet, vol.15, pp.259-271, 2014.

L. F. Duarte, Histone H3.3 and its proteolytically processed form drive a cellular senescence programme, Nat. Commun, vol.5, p.5210, 2014.

H. Chen, MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype, Mol. Cell, vol.59, pp.719-731, 2015.

B. C. Capell, Mll1 is essential for the senescenceassociated secretory phenotype, Genes Dev, vol.30, pp.321-336, 2016.

K. Contrepois, E. Ezan, C. Mann, and F. Fenaille, Ultra-high performance liquid chromatography-mass spectrometry for the fast profiling of histone posttranslational modifications, J. Proteome Res, vol.9, pp.5501-5509, 2010.

K. Contrepois, J. Thuret, R. Courbeyrette, F. Fenaille, and C. Mann, Deacetylation of H4-K16Ac and heterochromatin assembly in senescence, Epigenetics Chromatin, vol.5, p.15, 2012.
URL : https://hal.archives-ouvertes.fr/cea-01616195

S. P. Khare, HIstome-A relational knowledgebase of human histone proteins and histone modifying enzymes, Nucleic Acids Res, vol.40, pp.337-342, 2012.

H. Nishida, T. Suzuki, Y. Tomaru, and Y. Hayashizaki, A novel replicationindependent histone H2a gene in mouse, BMC Genet, vol.6, p.10, 2005.

R. Di-micco, Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication, Nature, vol.444, pp.638-642, 2006.

F. A. Mallette, M. F. Gaumont-leclerc, and G. Ferbeyre, The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence, Genes Dev, vol.21, pp.43-48, 2007.

M. Jeanblanc, Parallel pathways in RAF-induced senescence and conditions for its reversion, Oncogene, vol.31, pp.3072-3085, 2012.

C. J. Kemp, Multistep skin cancer in mice as a model to study the evolution of cancer cells, Semin. Cancer Biol, vol.15, pp.460-473, 2005.

D. Vindrieux, PLA2R1 mediates tumor suppression by activating JAK2, Cancer Res, vol.73, pp.6334-6345, 2013.

M. F. Lopez, Depletion of nuclear histone H2A variants is associated with chronic DNA damage signaling on drug-evoked senescence of human somatic cells, Aging, vol.4, pp.823-842, 2012.

M. E. Ritchie, Limma powers differential expression analyses for RNAsequencing and microarray studies, Nucleic Acids Res, vol.43, p.47, 2015.

A. Subramanian, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl Acad. Sci. USA, vol.102, pp.15545-15550, 2005.

F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani, Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability, Carcinogenesis, vol.30, pp.1073-1081, 2009.

S. Cornen, Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling, PLoS ONE, vol.9, p.81843, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01614950

J. Yao, Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression, Cancer Res, vol.66, pp.4065-4078, 2006.

A. Freund, A. V. Orjalo, P. Y. Desprez, and J. Campisi, Inflammatory networks during cellular senescence: causes and consequences, Trends Mol. Med, vol.16, pp.238-246, 2010.

P. V. Kharchenko, M. Y. Tolstorukov, and P. J. Park, Design and analysis of ChIP-seq experiments for DNA-binding proteins, Nat. Biotechnol, vol.26, pp.1351-1359, 2008.

M. Yukawa, Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells, PLoS ONE, vol.9, p.92689, 2014.

D. J. Baker, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature, vol.530, pp.184-189, 2016.

N. Schuler and C. E. Rübe, Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?, PLoS ONE, vol.8, p.63932, 2013.

C. Bönisch and S. B. Hake, Histone H2A variants in nucleosomes and chromatin: More or less stable?, Nucleic Acids Res, vol.40, pp.10719-10741, 2012.

F. Rodier, Persistent DNA damage signalling triggers senescenceassociated inflammatory cytokine secretion, Nat. Cell Biol, vol.11, pp.973-979, 2009.

N. Malaquin, A. Carrier-leclerc, M. Dessureault, and F. Rodier, DDR-mediated crosstalk between DNA-damaged cells and their microenvironment, Front. Genet, vol.5, p.94, 2015.

A. Freund, C. K. Patil, and J. Campisi, p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype, EMBO J, vol.30, pp.1536-1548, 2011.

I. Barde, P. Salmon, and D. Trono, Production and titration of lentiviral vectors, Curr. Protoc. Neurosci, vol.53, 2010.

B. A. Garcia, Chemical derivatization of histones for facilitated analysis by mass spectrometry, Nat. Protoc, vol.2, pp.933-938, 2007.

R. C. Gentleman, Bioconductor: open software development for computational biology and bioinformatics, Genome Biol, vol.5, p.80, 2004.

M. J. Dunning, M. L. Smith, M. E. Ritchie, and S. Tavaré, Beadarray: R classes and methods for Illumina bead-based data, Bioinformatics, vol.23, pp.2183-2184, 2007.

W. Shi, A. Oshlack, and G. K. Smyth, Optimizing the noise versus bias trade-off for Illumina whole genome expression BeadChips, Nucleic Acids Res, vol.38, p.204, 2010.

J. T. Leek, W. E. Johnson, H. S. Parker, A. E. Jaffe, and J. D. Storey, The SVA package for removing batch effects and other unwanted variation in highthroughput experiments, Bioinformatics, vol.28, pp.882-883, 2012.

J. Coppé, P. Desprez, A. Krtolica, and J. Campisi, The senescenceassociated secretory phenotype: the dark side of tumor suppression, Annu. Rev. Pathol, vol.5, pp.99-118, 2010.

E. Paradis, J. Claude, and K. Strimmer, APE: Analyses of phylogenetics and evolution in R language, Bioinformatics, vol.20, pp.289-290, 2004.
URL : https://hal.archives-ouvertes.fr/ird-01887318

S. Andrews and . Fastqc, A quality control tool for high throughput sequence data, 2010.

F. T. Krueger and !. Galore, , 2012.

M. Martin, Cutadapt removes adapter sequences from high-throughput sequencing reads, EMBnet.journal, vol.17, p.10, 2011.

D. Kim, TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions, Genome Biol, vol.14, p.36, 2013.

C. Trapnell, Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks, Nat. Protoc, vol.7, pp.562-578, 2012.

Y. Liao, G. K. Smyth, and W. Shi, FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features, Bioinformatics, vol.30, pp.923-930, 2014.

M. I. Love, S. Anders, and W. Huber, Differential analysis of count data -the DESeq2 package, Genome Biol, vol.15, p.550, 2014.

E. Aronesty, ea-utils: Command-line tools for processing biological sequencing data, 2011.

H. Li, Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM, 2013.

A. R. Quinlan and I. M. Hall, BEDTools: a flexible suite of utilities for comparing genomic features, Bioinformatics, vol.26, pp.841-842, 2010.

F. Ramírez, F. Dündar, S. Diehl, B. A. Grüning, and T. Manke, deepTools: a flexible platform for exploring deep-sequencing data, Nucleic Acids Res, vol.42, pp.187-191, 2014.

C. Acknowledgements, the Association pour la Recherche sur le Cancer, the Comité de l'Essonne de la Ligue Contre le Cancer, and the CEA Plasticity and Instability of the Genome Program. K.C. and C.C. were doctoral fellows in the CEA International PhD. Program (Irtelis). K.C, M. received funding from the Fondation pour la Recherche Médicale (DEP20131128527)

B. A. and N. C. , received funding from the German Research Foundation (RU 821/3-1) and the European Atomic Energy Community's Seventh Framework Programme (FP7/ 2007-2011) under grant agreement n° 249689 (Low Dose Research towards Multidisciplinary Integration). M.P.S. was funded by NIH grants 5P01GM09913005 and 5P50HG00773502. C.R. and W.M.B. were funded by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We thank Virginie Lavilla for help with qPCR experiments, the eBio platform

K. C. , F. F. , C. Coudereau, C. Carvalho, C. E. Redon et al., performed Illumina Bead Chip experiments, K.C. and Z.M. prepared RNA-seq libraries