Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation
Open accessAbstract
The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells, heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of presenescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks, nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.
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Senescence-associated heterochromatin foci are organized heterochromatic domains detected as dense DAPI-positive nuclear structures enriched in repressive marks and proteins including H3K9me3, HP1, HMGA factors, macroH2A, HIRA and ASF1A.
“Senescence-associated heterochromatin foci (SAHF) are spatially organized heterochromatic domains that can be detected as dense 4′,6-diamidino-2-phenylindole (DAPI)-positive nuclear structures that are enriched in repressive chromatin marks and proteins, including trimethylated histone H3 Lys9 (H3K9me3), heterochromatin protein 1 (HP1), high mobility group protein A (HMGA) factors, histone variant”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [51]
The Introduction describes SAHFs as DAPI-dense foci, and the Results (‘Multilayer Structure of Chromatin in SAHFs’; page not provided) show spatially organized H3K9me3-rich regions containing HP1γ. The paper also identifies HMGA1 as a structural component. Our copy does not establish enrichment of macroH2A, HIRA, or ASF1A in SAHFs; searches for those terms found no supporting passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHeterochromatin incorporated into SAHF results from redistribution of pre-existing repressive heterochromatin marks rather than newly formed heterochromatin on genomic regions.
“Heterochromatin incorporated into SAHF results from the redistribution of pre-existing repressive heterochromatin marks rather than newly formed heterochromatin on genomic regions [167,253,278,279].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [278]
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Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696 · see citing works
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898 · see citing works
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845 · see citing works
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129 · see citing works
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Bannister, A. J., Zegerman, P., Partridge, J. F., Miska, E. A., Thomas, J. O., Allshire, R. C., & Kouzarides, T. (2001) · Nature · doi:10.1038/35065138 · Cited by 2,903 · see citing works
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., & Jenuwein, T. (2001) · Nature · doi:10.1038/35065132 · Cited by 2,868 · see citing works
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · see citing works
Self-citationRole of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
Nakayama, J.-I., Rice, J. C., Strahl, B. D., Allis, C. D., & Grewal, S. I. S. (2001) · Science · doi:10.1126/science.1060118 · Cited by 1,739 · see citing works
Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse
Bernstein, B., Kamal, M., Lindblad‐Toh, K., Bekiranov, S., Bailey, D. K., Huebert, D. J., McMahon, S., Karlsson, E. K., Kulbokas, E. J., Gingeras, T., et al. (2005) · Cell · doi:10.1016/j.cell.2005.01.001 · Cited by 1,509 · see citing works
Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., & de Laat, W. (2006) · Nature Genetics · doi:10.1038/ng1896 · Cited by 1,386 · see citing works
Role of Histone H3 Lysine 27 Methylation in X Inactivation
Plath, K., Fang, J., Mlynarczyk‐Evans, S., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., & Zhang, Y. (2003) · Science · doi:10.1126/science.1084274 · Cited by 1,190 · see citing works
Beyond the Sequence: Cellular Organization of Genome Function
Misteli, T. (2007) · Cell · doi:10.1016/j.cell.2007.01.028 · Cited by 1,140 · see citing works
Chromosome TerritoriesPreprint
Cremer, T. J., & Cremer, M. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003889 · Cited by 1,115 · see citing works
Autophagy mediates the mitotic senescence transition
Young, A. R. J., Narita, M., Ferreira, M., Kirschner, K., Sadaie, M., Darot, J. F. J., Tavaré, S., Arakawa, S., Shimizu, S., Watt, F. M., et al. (2009) · Genes & Development · doi:10.1101/gad.519709 · Cited by 1,078 · see citing works
Self-citationA high-resolution map of active promoters in the human genome
Kim, T. H., Barrera, L., Zheng, M., Qu, C.-X., Singer, M. A., Richmond, T., Wu, Y. N., Green, R. D., & Ren, B. (2005) · Nature · doi:10.1038/nature03877 · Cited by 1,019 · see citing works
Systematic Protein Location Mapping Reveals Five Principal Chromatin Types in Drosophila Cells
Filion, G. J. P., van Bemmel, J. G., Braunschweig, U., Talhout, W., Kind, J., Ward, L. D., Brugman, W., de Castro, I. J., Kerkhoven, R. M., Bussemaker, H. J., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.009 · Cited by 963 · see citing works
Rb targets histone H3 methylation and HP1 to promoters
Nielsen, S. J., Schneider, R., Bauer, U., Bannister, A. J., Morrison, A. J., O’Carroll, D., Firestein, R., Cleary, M. L., Jenuwein, T., Herrera, R. E., et al. (2001) · Nature · doi:10.1038/35087620 · Cited by 901 · see citing works
Comprehensive analysis of the chromatin landscape in Drosophila melanogaster
Kharchenko, P. V., Alekseyenko, A. A., Schwartz, Y. B., Minoda, A., Riddle, N. C., Ernst, J., Sabo, P. J., Larschan, E., Gorchakov, A. A., Gu, T., et al. (2010) · Nature · doi:10.1038/nature09725 · Cited by 853 · see citing works
Histones: annotating chromatin
Campos, E. I., & Reinberg, D. (2009) · Annual Review of Genetics · doi:10.1146/annurev.genet.032608.103928 · Cited by 852 · see citing works
Distinct epigenomic landscapes of pluripotent and lineage-committed human cells
Hawkins, R. D., Hon, G. C., Lee, L. K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L. E., Kuan, S., Luu, Y., Klugman, S., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.03.018 · Cited by 806 · see citing works
Nuclear organization of the genome and the potential for gene regulation
Fraser, P., & Bickmore, W. (2007) · Nature · doi:10.1038/nature05916 · Cited by 734 · see citing works
Differential chromatin marking of introns and expressed exons by H3K36me3
Kolasinska-Zwierz, P., Down, T. A., Latorre, I. J., Liu, T., Liu, X. S., & Ahringer, J. (2009) · Nature Genetics · doi:10.1038/ng.322 · Cited by 671 · see citing works
Silva, J., Mak, W., Zvetkova, I., Appanah, R., Nesterova, T. B., Webster, Z., Peters, A. H. F. M., Jenuwein, T., Otte, A. P., & Brockdorff, N. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00068-6 · Cited by 638 · see citing works
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629 · see citing works
Self-citationCui, K., Zang, C., Roh, T., Schones, D. E., Childs, R. W., Peng, W., & Zhao, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.11.011 · Cited by 620 · see citing works
Facultative Heterochromatin: Is There a Distinctive Molecular Signature?
Trojer, P., & Reinberg, D. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.09.011 · Cited by 609 · see citing works
Ryba, T., Hiratani, I., Lu, J., Itoh, M., Kulik, M. J., Zhang, J., Schulz, T. C., Robins, A. J., Dalton, S., & Gilbert, D. M. (2010) · Genome Research · doi:10.1101/gr.099655.109 · Cited by 608 · see citing works
Self-citationCytogenetic analysis by chromosome painting using dop‐pcr amplified flow‐sorted chromosomes
Telenius, H., Ponder, B. A. J., Tunnacliffe, A., Pelmear, A., Carter, N. P., Ferguson-Smith, M. A., Behmel, A., Nordenskjöld, M., & Pfragner, R. (1992) · Genes Chromosomes and Cancer · doi:10.1002/gcc.2870040311 · Cited by 572 · see citing works
Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation
Hiratani, I., Ryba, T., Itoh, M., Yokochi, T., Schwaiger, M., Chang, C., Lyou, Y., Townes, T. M., Schübeler, D., & Gilbert, D. M. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060245 · Cited by 548 · see citing works
Self-citationMorgan, M. T., Anders, S., Lawrence, M. F., Aboyoun, P., Pagès, H., & Gentleman, R. C. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp450 · Cited by 545 · see citing works
ChIP-seq: Using high-throughput sequencing to discover protein–DNA interactions
Schmidt, D., Wilson, M. D., Spyrou, C., Brown, G. D., Hadfield, J., & Odom, D. T. (2009) · Methods · doi:10.1016/j.ymeth.2009.03.001 · Cited by 515 · see citing works
Self-citationAgger, K., Cloos, P. A. C., Rudkjær, L., Williams, K., Andersen, G., Christensen, J., & Helin, K. (2009) · Genes & Development · doi:10.1101/gad.510809 · Cited by 427 · see citing works
Molecular dissection of formation of senescence-associated heterochromatin foci
Zhang, R., Chen, W., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02019-06 · Cited by 415 · see citing works
Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence
Chicas, A., Wang, X., Zhang, C., McCurrach, M., Zhao, Z., Mert, O., Dickins, R. A., Narita, M., Zhang, M., & Lowe, S. W. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.023 · Cited by 388 · see citing works
Self-citationHistone demethylase JMJD3 contributes to epigenetic control of <i>INK4a/ARF</i> by oncogenic RAS
Barradas, M., Anderton, E., Acosta, J. C., Li, S., Banito, A., Rodriguez-Niedenführ, M., Maertens, G., Banck, M., Zhou, M.-M., Walsh, M. J., et al. (2009) · Genes & Development · doi:10.1101/gad.511109 · Cited by 352 · see citing works
Kimurâ, H., Hayashi‐Takanaka, Y., Goto, Y., Takizawa, N., & Nozaki, N. (2008) · Cell Structure and Function · doi:10.1247/csf.07035 · Cited by 296 · see citing works
Self-citationGlobal Chromatin Architecture Reflects Pluripotency and Lineage Commitment in the Early Mouse Embryo
Ahmed, K., Dehghani, H., Rugg‐Gunn, P. J., Fussner, E., Rossant, J., & Bazett‐Jones, D. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010531 · Cited by 264 · see citing works
Self-citationPauler, F. M., Sloane, M. A., Huang, R., Regha, K., Koerner, M. V., Tamir, I., Sommer, A., Aszódi, A., Jenuwein, T., & Barlow, D. P. (2008) · Genome Research · doi:10.1101/gr.080861.108 · Cited by 250 · see citing works
Loss of linker histone H1 in cellular senescence
Funayama, R., Saito, M., Tanobe, H., & Ishikawa, F. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200604005 · Cited by 241 · cited 4× · see citing works
“SAHFs represent single chromosomes (Zhang et al., 2007; Funayama et al., 2006).”
BackgroundInfluentialMultiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome
Chadwick, B. P., & Willard, H. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408021101 · Cited by 235 · see citing works
Hayashi‐Takanaka, Y., Yamagata, K., Wakayama, T., Stasevich, T. J., Kainuma, T., Tsurimoto, T., Tachibana, M., Shinkai, Y., Kurumizaka, H., Nozaki, N., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr343 · Cited by 227 · see citing works
Self-citationActivation of androgen receptor by histone demethylases JMJD2A and JMJD2D
Shin, S., & Janknecht, R. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.05.179 · Cited by 214 · see citing works
Self-citationReplication timing and transcriptional control: beyond cause and effect — part III
Rivera‐Mulia, J. C., & Gilbert, D. M. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.03.022 · Cited by 208 · see citing works
Self-citationDirect Imaging of DNA in Living Cells Reveals the Dynamics of Chromosome Formation
Manders, E. M. M., Kimurâ, H., & Cook, P. R. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.5.813 · Cited by 208 · see citing works
Regulation of heterochromatin by histone methylation and small RNAs
Grewal, S. I. S., & Rice, J. C. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.04.002 · Cited by 205 · see citing works
Clemson, C., Hall, L. L., Byron, M., McNeil, J. A., & Lawrence, J. B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601069103 · Cited by 203 · see citing works
A Suv39h‐dependent mechanism for silencing S‐phase genes in differentiating but not in cycling cells
Ait‐Si‐Ali, S., Guasconi, V., Fritsch, L., Yahi, H., Sekhri, R., Naguibneva, I., Robin, P., Cabon, F., Polesskaya, A., & Harel‐Bellan, A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600074 · Cited by 190 · see citing works
Adams, P. D. (2007) · Gene · doi:10.1016/j.gene.2007.04.020 · Cited by 174 · see citing works
Identifying dispersed epigenomic domains from ChIP-Seq data
Song, Q., & Smith, A. D. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr030 · Cited by 158 · see citing works
Shopland, L. S., Lynch, C. R., Peterson, K. A., Thornton, K. R., Kepper, N., Hase, J. V., Stein, S., Vincent, S., Molloy, K. R., Kreth, G., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200603083 · Cited by 149 · see citing works
The p400 E1A-associated protein is a novel component of the p53 → p21 senescence pathwayPreprint
Chan, H. M., Narita, M., Lowe, S. W., & Livingston, D. M. (2005) · Genes & Development · doi:10.1101/gad.1280205 · Cited by 144 · see citing works
Self-citationReplication timing and transcriptional control: beyond cause and effect--part II
Hiratani, I., Takebayashi, S.-I., Lu, J., & Gilbert, D. M. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.02.002 · Cited by 140 · see citing works
Self-citationIdentification of higher-order functional domains in the human ENCODE regionsPreprint
Thurman, R. E., Day, N., Noble, W. S., & Stamatoyannopoulos, J. A. (2007) · Genome Research · doi:10.1101/gr.6081407 · Cited by 134 · see citing works
Hayashi‐Takanaka, Y., Yamagata, K., Nozaki, N., & Kimurâ, H. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200904137 · Cited by 133 · see citing works
Self-citationArchidiacono, N., Antonacci, R., Marzella, R., Finelli, P., Lonoce, A., & Rocchi, M. (1995) · Genomics · doi:10.1016/0888-7543(95)80048-q · Cited by 114 · see citing works
Weddington, N., Stuy, A., Hiratani, I., Ryba, T., Yokochi, T., & Gilbert, D. M. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-530 · Cited by 83 · see citing works
Self-citationVisualization of genomic data with the Hilbert curve
Anders, S. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp152 · Cited by 76 · see citing works
FISH on three-dimensionally preserved nuclei
Solovei, I. V., Walter, J., Cremer, M., Habermann, F. A., Schermelleh, L., & Cremer, T. J. (2002) · doi:10.1093/oso/9780199638833.003.0007 · Cited by 70 · see citing works
Chadwick, B. P. (2006) · Chromosoma · doi:10.1007/s00412-006-0085-1 · Cited by 50 · see citing works
Sinclair, P. B., Bian, Q., Plutz, M., Heard, É., & Belmont, A. S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200912167 · Cited by 35 · see citing works
Global re‐organization of replication domains during embryonic stem cell differentiation
Gilbert, D. M., Hiratani, I., Hiratani, M., et al. (2009) · The FASEB Journal · doi:10.1096/fasebj.23.1_supplement.481.1 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
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Sorted by citations
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104 · see citing works
Epigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956 · see citing works
Cellular senescence and its effector programs
Salama, R., Sadaie, M., Hoare, M., & Narita, M. (2014) · Genes & Development · doi:10.1101/gad.235184.113 · Cited by 855 · see citing works
Self-citationAutophagy mediates degradation of nuclear lamina
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., et al. (2015) · Nature · doi:10.1038/nature15548 · Cited by 655 · see citing works
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588 · see citing works
Shah, P. P., Donahue, G., Otte, G. L., Capell, B. C., Nelson, D. M., Cao, K., Aggarwala, V., Cruickshanks, H. A., Rai, T. S., McBryan, T., et al. (2013) · Genes & Development · doi:10.1101/gad.223834.113 · Cited by 550 · see citing works
Mechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506 · see citing works
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
Comparative analysis of metazoan chromatin organization
Ho, J. W. K., Jung, Y. L., Liu, T., Alver, B. H., Lee, S., Ikegami, K., Sohn, K.-A., Minoda, A., Tolstorukov, M. Y., Appert, A., et al. (2014) · Nature · doi:10.1038/nature13415 · Cited by 390 · see citing works
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Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408 · see citing works
“31).”
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Cruickshanks, H. A., McBryan, T., Nelson, D. M., VanderKraats, N. D., Shah, P. P., van Tuyn, J., Singh Rai, T., Brock, C., Donahue, G., Dunican, D. S., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2879 · Cited by 358 · see citing works
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Chandra, T., Ewels, P. A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S. W., Kirschner, K., Thuret, J.-Y., Andrews, S., Fraser, P., & Reik, W. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.055 · Cited by 348 · see citing works
Self-citationSadaie, M., Salama, R., Carroll, T., Tomimatsu, K., Chandra, T., Young, A. R. J., Narita, M., Pérez-Mancera, P. A., Bennett, D. C., Chong, H., et al. (2013) · Genes & Development · doi:10.1101/gad.217281.113 · Cited by 323 · see citing works
Self-citationSwanson, E. C., Manning, B., Zhang, H., & Lawrence, J. B. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201306073 · Cited by 251 · see citing works
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247 · see citing works
Chen, H., Ruiz, P. D., McKimpson, W. M., Novikov, L., Kitsis, R. N., & Gamble, M. J. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.011 · Cited by 205 · see citing works
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Aird, K. M., Iwasaki, O., Kossenkov, A. V., Tanizawa, H., Fatkhutdinov, N., Bitler, B. G., Le, L., Alicea, G., Yang, T.-L., Johnson, F. B., et al. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201608026 · Cited by 175 · see citing works
Rai, T. S., Cole, J. J., Nelson, D. M., Dikovskaya, D., Faller, W. J., Vizioli, M. G., Hewitt, R. N., Anannya, O., McBryan, T., Manoharan, I., et al. (2014) · Genes & Development · doi:10.1101/gad.247528.114 · Cited by 162 · see citing works
4D Genome Rewiring during Oncogene-Induced and Replicative Senescence
Sati, S., Bonev, B., Szabo, Q., Jost, D., Bensadoun, P., Serra, F., Loubiere, V., Papadopoulos, G. L., Rivera-Mulia, J.-C., Fritsch, L., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.007 · Cited by 170 · see citing works
Self-citationGenetic and epigenetic regulation of human aging and longevity
Morris, B. J., Willcox, B. J., & Donlon, T. A. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.039 · Cited by 140 · see citing works
The Chromatin Landscape of Cellular Senescence
Criscione, S. W., Teo, Y. V., & Neretti, N. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.09.005 · Cited by 137 · see citing works
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116 · see citing works
Quantitation and Identification of Thousands of Human Proteoforms below 30 kDa
Durbin, K. R., Fornelli, L., Fellers, R. T., Doubleday, P. F., Narita, M., & Kelleher, N. L. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00997 · Cited by 111 · see citing works
Self-citationNOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence
Parry, A. J., Hoare, M., Bihary, D., Hänsel-Hertsch, R., Smith, S., Tomimatsu, K., Mannion, E., Smith, A., D’Santos, P., Russell, I. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04283-9 · Cited by 102 · see citing works
Self-citationChromatin basis of the senescence-associated secretory phenotype
Hao, X., Wang, C., & Zhang, R. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.003 · Cited by 94 · see citing works
Nuclear pore density controls heterochromatin reorganization during senescence
Boumendil, C., Hari, P., Olsen, K. C. F., Acosta, J. C., & Bickmore, W. A. (2019) · Genes & Development · doi:10.1101/gad.321117.118 · Cited by 89 · see citing works
Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence.
Lenain, C., de Graaf, C. A., Pagie, L., Visser, N. L., de Haas, M., de Vries, S. S., Peric-Hupkes, D., van Steensel, B., & Peeper, D. S. (2017) · Genome Research · doi:10.1101/gr.225763.117 · Cited by 89 · see citing works
Takebayashi, S., Tanaka, H., Hino, S., Nakatsu, Y., Igata, T., Sakamoto, A., Narita, M., & Nakao, M. (2015) · Aging Cell · doi:10.1111/acel.12351 · Cited by 84 · see citing works
Self-citationShort-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80 · see citing works
Self-citationDetection of senescence using machine learning algorithms based on nuclear features
Duran, I., Pombo, J., Sun, B., Gallage, S., Kudo, H., McHugh, D., Bousset, L., Barragan Avila, J. E., Forlano, R., Manousou, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45421-w · Cited by 85 · see citing works
ATF3 drives senescence by reconstructing accessible chromatin profiles
Zhang, C., Zhang, X., Huang, L., Guan, Y., Huang, X., Tian, X., Zhang, L., & Tao, W. (2021) · Aging Cell · doi:10.1111/acel.13315 · Cited by 84 · see citing works
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence
Olan, I., Parry, A. J., Schoenfelder, S., Narita, M., Ito, Y., Chan, A. S. L., Slater, G. S. C., Bihary, D., Bando, M., Shirahige, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19878-4 · Cited by 76 · see citing works
Self-citationDOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A
Leon, K. E., Buj, R., Lesko, E., Dahl, E. S., Chen, C.-W., Tangudu, N. K., Imamura-Kawasawa, Y., Kossenkov, A. V., Hobbs, R. P., & Aird, K. M. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202008101 · Cited by 70 · see citing works
Epigenetic regulation in cell senescence
Cheng, L.-Q., Zhang, Z.-Q., Chen, H.-Z., & Liu, D.-P. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1581-x · Cited by 64 · see citing works
Goronzy, J. J., Hu, B., Kim, C., Jadhav, R. R., & Weyand, C. M. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ri0418-160r · Cited by 60 · see citing works
Iwasaki, O., Tanizawa, H., Kim, K.-D., Kossenkov, A., Nacarelli, T., Tashiro, S., Majumdar, S., Showe, L. C., Zhang, R., & Noma, K.-I. (2019) · Nature Communications · doi:10.1038/s41467-019-13604-5 · Cited by 58 · see citing works
Old cells, new tricks: chromatin structure in senescence
Parry, A. J., & Narita, M. (2016) · Mammalian Genome · doi:10.1007/s00335-016-9628-9 · Cited by 53 · see citing works
Self-citationPemberton, H., Anderton, E., Patel, H., Brookes, S., Chandler, H., Palermo, R., Stock, J., Rodriguez-Niedenführ, M., Racek, T., de Breed, L., et al. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r23 · Cited by 50 · see citing works
Isermann, A., Mann, C., & Rübe, C. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239130 · Cited by 54 · see citing works
Cholangiokines: undervalued modulators in the hepatic microenvironment
Cai, X., Tacke, F., Guillot, A., & Liu, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1192840 · Cited by 40 · see citing works
The functional impact of nuclear reorganization in cellular senescence
Rocha, A., Dalgarno, A., & Neretti, N. (2022) · Briefings in Functional Genomics · doi:10.1093/bfgp/elab012 · Cited by 38 · see citing works
Advancing biological understanding of cellular senescence with computational multiomics
Li, S., Agudelo Garcia, P. A., Aliferis, C., Becich, M. J., Calyeca, J., Cosgrove, B. D., Elisseeff, J., Farzad, N., Fertig, E. J., Glass, C., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02314-y · Cited by 40 · see citing works
Locus-specific induction of gene expression from heterochromatin loci during cellular senescence
Tomimatsu, K., Bihary, D., Olan, I., Parry, A. J., Schoenfelder, S., Chan, A. S. L., Slater, G. S. C., Ito, Y., Rugg-Gunn, P. J., Kirschner, K., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00147-y · Cited by 25 · see citing works
Self-citation
- Authors
- Chandra, T., Kirschner, K., Thuret, J.-Y., Pope, B. D., Ryba, T., Newman, S., Ahmed, K., Samarajiwa, S. A., Salama, R., Carroll, T., Stark, R., Janky, R., Narita, M., Xue, L., Chicas, A., Nũnez, S., Janknecht, R., Hayashi-Takanaka, Y., Wilson, M. D., Marshall, A., Odom, D. T., Babu, M. M., Bazett-Jones, D. P., Tavaré, S., Edwards, P. A. W., Lowe, S. W., Kimura, H., Gilbert, D. M., & Narita, M.
- Affiliations
- University of Cambridge (GB)
- Cancer Research UK (GB)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Florida State University (US)
- Hospital for Sick Children (CA)
- MRC Laboratory of Molecular Biology (GB)
- Memorial Sloan Kettering Cancer Center (US)
- University of Oklahoma Health Sciences Center (US)
- The University of Osaka (JP)
- Corresponding author
- Narita, Masashi
- ORCID
- Chandra, Tamir
- Kirschner, Kristina
- Thuret, Jean-Yves
- Pope, Benjamin D.
- Ryba, Tyrone
- Newman, Scott
- Ahmed, Kashif
- Samarajiwa, Shamith A.
- Salama, Rafik
- Carroll, Thomas
- Stark, Rory
- Janky, Rekin's
- Narita, Masako
- Xue, Lixiang
- Janknecht, Ralf
- Wilson, Michael D.
- Marshall, Aileen
- Odom, Duncan T.
- Babu, M. Madan
- Tavaré, Simon
- Edwards, Paul A.W.
- Lowe, Scott W.
- Gilbert, David M.
- Narita, Masashi
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 47
- Issue
- 2
- Pages
- 203-214
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3701408
- OpenAlex
- W2153643905
- Cited by
- 308
- References
- 63
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 28 · 2023: 17 · 2022: 20 · 2021: 23 · 2020: 29 · 2019: 19 · 2018: 24 · 2017: 19 · 2016: 22 · 2015: 28 · 2014: 26 · 2013: 27 · 2012: 5
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- Cancer Research UK (14545, 19556, 15890, 15603, A15603)
- Canadian Institutes of Health Research
- Japan Society for the Promotion of Science (22370063)
- National Institute on Aging (R01AG016379)
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (GM083337, P01GM085354, GM085354, R01GM083337)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- heterochromatin formation, H3K9me3, H3K27me3, chromatin condensation, epigenetic remodeling, DNA replication timing, fibroblast senescence, histone occupancy
- MeSH terms
- Bromodeoxyuridine, Chromatin, Chromosomes, Fibroblasts, Heterochromatin, Histones, Humans, Microscopy, Fluorescence, Genome, Cellular Senescence, Gene Expression Regulation, Developmental, Gene Silencing, Epigenesis, Genetic, Laser Scanning Cytometry, Genome-Wide Association Study
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