Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression

Nature Communications - Tập 8 Số 1
Kévin Contrepois1, Clément Coudereau1, Bérénice A. Benayoun2, Nadine Schuler3, Pierre‐François Roux4, Oliver Bischof4, Rëgis Courbeyrette1, Cyril Carvalho1, Jean‐Yves Thuret1, Zhihai Ma2, Céline Derbois5, Marie‐Claire Nevers6, Hervé Volland6, Christophe E. Redon7, William M. Bonner7, Jean‐François Deleuze5, Clotilde Wiel8, David Bernard8, M Snyder2, Claudia E. Rübe3, Robert Olaso5, François Fenaille9, Carl Mann1
1Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex, 91198, France
2Department of Genetics, Stanford University, Stanford, 94305-5120, California, USA
3Department of Radiation Oncology, Saarland University, 66421 Homburg (Saar), Germany
4Department of Cell Biology and Infection, Institut Pasteur/INSERM U933, Laboratory of Nuclear Organization and Oncogenesis, Paris, 75015, France
5CEA, CNG, Evry, 91057, France
6CEA, Service de Pharmacologie et Immunoanalyse (SPI), INRA, Université Paris-Saclay, Gif-sur-Yvette, F-91191, France
7Laboratory of Molecular Pharmacology, C.C.R., N.C.I., N.I.H., Bethesda, 20892, Maryland, USA
8Inserm U1052, Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Centre Léon Bérard, Université de Lyon, 69008, Lyon, France
9CEA, IBITECS, Service de Pharmacologie et d'Immunoanalyse, UMR 0496, Laboratoire d'Etude du Métabolisme des Médicaments, MetaboHUB-Paris, Université Paris Saclay, Gif-sur-Yvette cedex, F-91191, France

Tóm tắt

AbstractThe senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J also accumulates in mice with aging in a tissue-specific manner and in human skin. Knock-down of H2A.J inhibits the expression of inflammatory genes that contribute to the senescent-associated secretory phenotype (SASP), and over expression of H2A.J increases the expression of some of these genes in proliferating cells. H2A.J accumulation may thus promote the signalling of senescent cells to the immune system, and it may contribute to chronic inflammation and the development of aging-associated diseases.

Từ khóa


Tài liệu tham khảo

Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685–705 (2013).

Collado, M. & Serrano, M. Senescence in tumours: evidence from mice and humans. Nat. Rev. Cancer 10, 51–57 (2010).

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

Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014).

Sagiv, A. & Krizhanovsky, V. Immunosurveillance of senescent cells: The bright side of the senescence program. Biogerontology 14, 617–628 (2013).

van Deursen, J. M. The role of senescent cells in ageing. Nature 509, 439–446 (2014).

Rai, T. S. & Adams, P. D. Lessons from senescence: Chromatin maintenance in non-proliferating cells. Biochim. Biophys. Acta 1819, 322–331 (2012).

Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes Dev. 28, 99–114 (2014).

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

Talbert, P. B. & Henikoff, S. Histone variants—ancient wrap artists of the epigenome. Nat. Rev. Mol. Cell Biol. 11, 264–275 (2010).

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

Duarte, L. F. et al. Histone H3.3 and its proteolytically processed form drive a cellular senescence programme. Nat. Commun. 5, 5210 (2014).

Chen, H. et al. MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol. Cell 59, 719–731 (2015).

Capell, B. C. et al. Mll1 is essential for the senescenceassociated secretory phenotype. Genes Dev. 30, 321–336 (2016).

Contrepois, K., Ezan, E., Mann, C. & Fenaille, F. Ultra-high performance liquid chromatography-mass spectrometry for the fast profiling of histone post-translational modifications. J. Proteome Res. 9, 5501–5509 (2010).

Contrepois, K., Thuret, J.-Y., Courbeyrette, R., Fenaille, F. & Mann, C. Deacetylation of H4-K16Ac and heterochromatin assembly in senescence. Epigenetics Chromatin 5, 15 (2012).

Khare, S. P. et al. HIstome-A relational knowledgebase of human histone proteins and histone modifying enzymes. Nucleic Acids Res. 40, D337–D342 (2012).

Nishida, H., Suzuki, T., Tomaru, Y. & Hayashizaki, Y. A novel replication-independent histone H2a gene in mouse. BMC Genet. 6, 10 (2005).

Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006).

Mallette, F. A., Gaumont-Leclerc, M. F. & Ferbeyre, G. The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev. 21, 43–48 (2007).

Jeanblanc, M. et al. Parallel pathways in RAF-induced senescence and conditions for its reversion. Oncogene 31, 3072–3085 (2012).

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

Vindrieux, D. et al. PLA2R1 mediates tumor suppression by activating JAK2. Cancer Res. 73, 6334–6345 (2013).

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

Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

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

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

Cornen, S. et al. Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. PLoS ONE 9, e81843 (2014).

Yao, J. et al. Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res. 66, 4065–4078 (2006).

Freund, A., Orjalo, A. V., Desprez, P. Y. & Campisi, J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16, 238–246 (2010).

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

Yukawa, M. et al. Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells. PLoS ONE 9, e92689 (2014).

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

Schuler, N. & Rübe, C. E. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging? PLoS ONE 8, e63932 (2013).

Bönisch, C. & Hake, S. B. Histone H2A variants in nucleosomes and chromatin: More or less stable? Nucleic Acids Res. 40, 10719–10741 (2012).

Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009).

Malaquin, N., Carrier-Leclerc, A., Dessureault, M. & Rodier, F. DDR-mediated crosstalk between DNA-damaged cells and their microenvironment. Front. Genet. 5, 94 (2015).

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

Barde, I., Salmon, P. & Trono, D. Production and titration of lentiviral vectors. Curr. Protoc. Neurosci. 53, 4.21.1–4.21.23 (2010).

Garcia, B. A. et al. Chemical derivatization of histones for facilitated analysis by mass spectrometry. Nat. Protoc. 2, 933–938 (2007).

Gentleman, R. C. et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).

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

Shi, W., Oshlack, A. & Smyth, G. K. Optimizing the noise versus bias trade-off for Illumina whole genome expression BeadChips. Nucleic Acids Res. 38, e204 (2010).

Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E. & Storey, J. D. The SVA package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28, 882–883 (2012).

Coppé, J.-P., Desprez, P.-Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).

Paradis, E., Claude, J. & Strimmer, K. APE: Analyses of phylogenetics and evolution in R language. Bioinformatics 20, 289–290 (2004).

Andrews, S. FastQC: A quality control tool for high throughput sequence data. Available at http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (2010).

Krueger, F. Trim Galore! Available at http://www.bioinformatics.babraham.ac.uk/projects/trim_galore/ (2012).

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

Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).

Trapnell, C. et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562–578 (2012).

Liao, Y., Smyth, G. K. & Shi, W. FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).

Love, M. I., Anders, S. & Huber, W. Differential analysis of count data - the DESeq2 package. Genome Biol. 15, 550 (2014).

Aronesty, E. ea-utils: Command-line tools for processing biological sequencing data. https://github.com/ExpressionAnalysis/ea-utils (2011).

Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at http://arXiv.org/abs/1303.3997 (2013).

Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

Ramírez, F., Dündar, F., Diehl, S., Grüning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187–W191 (2014).