Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence
Open accessAbstract
Accumulation of senescent cells during aging contributes to chronic inflammation and age-related diseases. While senescence is associated with profound alterations of the epigenome, a systematic view of epigenetic factors in regulating senescence is lacking. Here, we curated a library of short hairpin RNAs for targeted silencing of all known epigenetic proteins and performed a high-throughput screen to identify key candidates whose downregulation can delay replicative senescence of primary human cells. This screen identified multiple new players including the histone acetyltransferase p300 that was found to be a primary driver of the senescent phenotype. p300, but not the paralogous CBP, induces a dynamic hyper-acetylated chromatin state and promotes the formation of active enhancer elements in the non-coding genome, leading to a senescence-specific gene expression program. Our work illustrates a causal role of histone acetyltransferases and acetylation in senescence and suggests p300 as a potential therapeutic target for senescence and age-related diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genome-wide analysis of H3K4me3, H3K27me3 and H3K27ac in senescent cells reveals dynamic acquisition and depletion of large-scale chromatin domains proposed to regulate key senescence downstream effectors.
“Genome-wide analysis of H3 Lys4 trimethylation, H3 Lys27 trimethylation and H3 Lys27 acetylation in senescent cells has also revealed the dynamic acquisition and depletion of large-scale chromatin domains that have been proposed to regulate the expression of key senescence downstream effectors68–72”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [72]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new look at the statistical model identification
Akaike, H. (1974) · IEEE Transactions on Automatic Control · doi:10.1109/tac.1974.1100705 · Cited by 51,879 · see citing works
The ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223 · see citing works
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · see citing works
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302 · see citing works
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1× · see citing works
“…senescence in culture(Aliper et al., 2015), (3) targeted elimination of senescent cells extends healthspan and lifespan in mice(Baker et al., 2016; Baker et al., 2011), (4) “senolytic” compounds that induce senescent cell death show lifespan extension and therapeutic benefits in several…”
BackgroundSuper-enhancers in the control of cell identity and disease
Hnisz, D., Abraham, B. J., Lee, T. I., Lau, A., Saint-André, V., Sigova, A. A., Hoke, H. A., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.09.053 · Cited by 3,662 · see citing works
Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
Lovén, J., Hoke, H. A., Lin, C. Y., Lau, A., Orlando, D. A., Vakoc, C. R., Bradner, J. E., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.036 · Cited by 2,961 · see citing works
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · 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 · cited 3× · see citing works
“The latter include senescence-associated heterochromatic foci (SAHF)(Narita et al., 2003), inappropriate euchromatin(Shah et al., 2013) and chromatin fragmentation with cytoplasmic extrusion(Dou et al., 2017; Dou et al., 2015; Ivanov et al., 2013).”
BackgroundA unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233 · see citing works
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
Zuber, J., Shi, J., Wang, E., Rappaport, A. R., Herrmann, H., Sison, E. A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., et al. (2011) · Nature · doi:10.1038/nature10334 · Cited by 1,870 · see citing works
Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766 · see citing works
ChIP-seq accurately predicts tissue-specific activity of enhancers
Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., et al. (2009) · Nature · doi:10.1038/nature07730 · Cited by 1,639 · see citing works
DNA Damage Foci at Dysfunctional Telomeres
Takai, H., Smogorzewska, A., & de Lange, T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00542-6 · Cited by 1,409 · see citing works
Cytoplasmic chromatin triggers inflammation in senescence and cancer
Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. (2017) · Nature · doi:10.1038/nature24050 · Cited by 1,335 · see citing works
Self-citationAutophagy 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
Cellular senescence: a translational perspective
Kirkland, J. L., & Tchkonia, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.013 · Cited by 1,013 · 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
Self-citationCREB-binding Protein and p300 in Transcriptional Regulation
Vo, N., & Goodman, R. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r000025200 · Cited by 868 · see citing works
Chapuy, B., McKeown, M. R., Lin, C. Y., Monti, S., Roemer, M. G. M., Qi, J., Rahl, P. B., Sun, H. H., Yeda, K. T., Doench, J. G., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.11.003 · Cited by 735 · see citing works
Enhancers as non-coding RNA transcription units: recent insights and future perspectives
Li, W., Notani, D., & Rosenfeld, M. G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.4 · Cited by 710 · see citing works
Autophagy 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
Self-citationIyer, N. G., Özdağ, H., & Caldas, C. (2004) · Oncogene · doi:10.1038/sj.onc.1207118 · Cited by 645 · see citing works
Protein Lysine Acetylation by p300/CBP
Rabbitts, B. M., & Cole, P. A. (2015) · Chemical Reviews · doi:10.1021/cr500452k · Cited by 620 · see citing works
The interplay of epigenetic marks during stem cell differentiation and development
Atlasi, Y., & Stunnenberg, H. G. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.57 · Cited by 569 · 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
Self-citationLysosome-mediated processing of chromatin in senescence
Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., Shah, P. P., Hewitt, G., Korolchuk, V. I., Passos, J. F., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212110 · Cited by 539 · see citing works
Self-citationThe biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538 · see citing works
Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome
Weinert, B. T., Narita, T., Satpathy, S., Srinivasan, B., Hansen, B. K., Scholz, C. W., Hamilton, W. B., Zucconi, B. E., Wang, W., Liu, W. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.04.033 · Cited by 514 · see citing works
Mahat, D. B., Kwak, H., Booth, G. T., Jonkers, I. H., Danko, C. G., Patel, R. K., Waters, C. T., Munson, K. M., Core, L. J., & Lis, J. T. (2016) · Nature Protocols · doi:10.1038/nprot.2016.086 · Cited by 492 · see citing works
Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres
O'Sullivan, R. J., Kubicek, S., Schreiber, S. L., & Karlseder, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1897 · Cited by 416 · see citing works
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415 · cited 8× · see citing works
“0001 (Figure S4C-D and TS7) based on stringent criteria reported previously(Tasdemir et al., 2016).”
BackgroundResultInfluentialA Human Gene Responsible for Zellweger Syndrome That Affects Peroxisome Assembly
Shimozawa, N., Tsukamoto, T., Suzuki, Y., Orii, T., Shirayoshi, Y., Mori, T., & Fujiki, Y. (1992) · Science · doi:10.1126/science.1546315 · Cited by 361 · see citing works
Manifestations and mechanisms of stem cell aging
Liu, L. A., & Rando, T. A. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201010131 · Cited by 306 · see citing works
Cheng, J. B., & Russell, D. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406225200 · Cited by 270 · see citing works
Sidoli, S., Bhanu, N. V., Karch, K. R., Wang, X., & Garcia, B. A. (2016) · Journal of Visualized Experiments · doi:10.3791/54112 · Cited by 215 · see citing works
Self-citationGenetics and epigenetics of aging and longevity
Moskalev, A., Aliper, A. M., Smit‐McBride, Z., Buzdin, A. A., & Zhavoronkov, A. A. (2014) · Cell Cycle · doi:10.4161/cc.28433 · Cited by 187 · see citing works
The Metabolic Impact on Histone Acetylation and Transcription in Ageing
Peleg, S., Feller, C., Ladurner, A. G., & Imhof, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.05.008 · Cited by 178 · see citing works
Valor, L. M., Viosca, J., López‐Atalaya, J. P., & Barco, Á. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990382 · Cited by 168 · 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
Self-citationSims, D., Mendes‐Pereira, A. M., Frankum, J. R., Burgess, D. J., Cerone, M. A., Naceur‐Lombardelli, C., Mitsopoulos, C., Hakas, J., Murugaesu, N., Isacke, C. M., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-10-r104 · Cited by 124 · see citing works
Differentiation between Senescence (M1) and Crisis (M2) in Human Fibroblast Cultures
Wei, W., & Sedivy, J. M. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4665 · Cited by 109 · see citing works
Yuan, Z., Lin, S., Molden, R. C., Cao, X.-J., Bhanu, N. V., Wang, X., Sidoli, S., Liu, S., & Garcia, B. A. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.046011 · Cited by 108 · see citing works
Self-citationNelson, D. M., Jaber‐Hijazi, F., Cole, J. J., Robertson, N., Pawlikowski, J. S., Norris, K., Criscione, S. W., Pchelintsev, N. A., Piscitello, D., Stong, N., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1017-x · Cited by 103 · see citing works
Self-citationThe NADPH oxidase Nox4 restricts the replicative lifespan of human endothelial cells
Lener, B., Kozieł, R., Pircher, H., Hütter, E., Greussing, R., Herndler‐Brandstetter, D., Hermann, M., Unterluggauer, H., & Jansen‐Dürr, P. (2009) · Biochemical Journal · doi:10.1042/bj20090666 · Cited by 97 · see citing works
Next-generation libraries for robust RNA interference-based genome-wide screens
Kampmann, M., Horlbeck, M. A., Chen, Y., Tsai, J. C., Bassik, M. C., Gilbert, L. A., Villalta, J. E., Kwon, S. C., Chang, H., Kim, V. N., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508821112 · Cited by 93 · see citing works
Cellular Senescence and Tissue Aging In Vivo
Hornsby, P. J. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.7.b251 · Cited by 91 · see citing works
Tumor suppression by p53: making cells senescent.
Qian, Y., & Chen, X. (2010) · PubMed · doi:10.14670/hh-25.515 · Cited by 85 · see citing works
Aliper, A. M., Csoka, A. B., Buzdin, A. A., Jetka, T., Roumiantsev, S. A., Moskalev, A., & Zhavoronkov, A. A. (2015) · Aging · doi:10.18632/aging.100717 · Cited by 77 · see citing works
Sidoli, S., Simithy, J., Karch, K. R., Kulej, K., & Garcia, B. A. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b03009 · Cited by 61 · see citing works
Self-citation
Flagged first, then by citations
2 of the 54 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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
Epigenetic regulation of aging: implications for interventions of aging and diseases
Kang, W., Liu, H., Hu, Q., Wang, L., Liu, J., Zheng, Z., Zhang, W., Ren, J., Zhu, F., & Liu, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01211-8 · Cited by 694 · see citing works
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442 · see citing works
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 410 · see citing works
Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies
Weng, Z., Wang, Y., Ouchi, T., Liu, H., Qiao, X., Wu, C., Zhao, Z., Li, L., & Li, B. (2022) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac004 · Cited by 291 · see citing works
Chen, Q., Yang, B.-H., Liu, X., Zhang, X. D., Zhang, L., & Liu, T. (2022) · Theranostics · doi:10.7150/thno.73223 · Cited by 272 · see citing works
Self-citationHistone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells
Zhang, T., Zhang, Z., Dong, Q., Xiong, J., & Zhu, B. (2020) · Genome Biology · doi:10.1186/s13059-020-01957-w · Cited by 266 · see citing works
AP-1 imprints a reversible transcriptional programme of senescent cells.
Martínez-Zamudio, R. I., Roux, P.-F., de Freitas, J. A. N. L. F., Robinson, L., Doré, G., Sun, B., Belenki, D., Milanovic, M., Herbig, U., Schmitt, C. A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0529-5 · Cited by 236 · see citing works
Epigenetics of Aging and Aging-Associated Diseases
Saul, D., & Kosinsky, R. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010401 · Cited by 241 · see citing works
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan
Bradshaw, P. C. (2021) · Antioxidants · doi:10.3390/antiox10040572 · Cited by 185 · see citing works
A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence
Wang, W., Zheng, Y., Sun, S., Li, W., Song, M., Ji, Q., Wu, Z., Liu, Z., Fan, Y., Liu, F., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd2655 · Cited by 183 · see citing works
Dietary regulation in health and disease
Wu, Q., Gao, Z., Yu, X., & Wang, P. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01104-w · Cited by 182 · see citing works
EP300 Selectively Controls the Enhancer Landscape of MYCN -Amplified Neuroblastoma
Durbin, A. D., Wang, T., Wimalasena, V. K., Zimmerman, M. W., Li, D., Dharia, N. V., Mariani, L., Shendy, N. A. M., Nance, S., Patel, A. G., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0385 · Cited by 174 · see citing works
Ma, L., Gao, Z., Wu, J., Zhong, B., Xie, Y., Huang, W., & Lin, Y. (2021) · Molecules and Cells · doi:10.1016/j.molcel.2021.01.031 · Cited by 138 · see citing works
Watt, A. C. S., & Goel, S. (2022) · Breast Cancer Research · doi:10.1186/s13058-022-01510-6 · Cited by 151 · see citing works
Putting the brakes on the cell cycle: mechanisms of cellular growth arrest
Pack, L. R., Daigh, L. H., & Meyer, T. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.05.005 · Cited by 130 · see citing works
Epigenetic Regulation of Cellular Senescence
Crouch, J. D., Shvedova, M., Thanapaul, R. J. R. S., Botchkarev, V. A., & Roh, D. S. (2022) · Cells · doi:10.3390/cells11040672 · Cited by 132 · see citing works
Disease-associated astrocyte epigenetic memory promotes CNS pathology
Lee, H., Rone, J. M., Li, Z., Akl, C. F., Shin, S., Lee, J.-H., Flausino, L. E., Pernin, F., Chao, C., Kleemann, K. L., et al. (2024) · Nature · doi:10.1038/s41586-024-07187-5 · Cited by 135 · see citing works
Epigenetic Mechanisms of Aging and Aging-Associated Diseases
la Torre, A., Vecchio, F. L., & Greco, A. (2023) · Cells · doi:10.3390/cells12081163 · Cited by 120 · see citing works
Targeting post-translational histone modifying enzymes in glioblastoma
Kunadis, E., Lakiotaki, E., Korkolopoulou, P. A., & Piperi, C. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107721 · Cited by 111 · see citing works
Watt, A. C. S., Cejas, P., DeCristo, M. J., Metzger, O., Lam, E. Y. N., Qiu, X., BrinJones, H., Kesten, N., Coulson, R. S., Font‐Tello, A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-00135-y · Cited by 108 · see citing works
The TGF-β1/p53/PAI-1 Signaling Axis in Vascular Senescence: Role of Caveolin-1
Samarakoon, R., Higgins, S. P., Higgins, C. E., & Higgins, P. J. (2019) · Biomolecules · doi:10.3390/biom9080341 · Cited by 102 · see citing works
The Histone Code of Senescence
Paluvai, H., Giorgio, E. D., & Brancolini, C. (2020) · Cells · doi:10.3390/cells9020466 · Cited by 94 · 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
“Recently, a RNAi screening of epigenetic proteins indicated that p300 drives senescence mediated by de novo super enhancer formation(P. Sen et al., 2019).”
BackgroundThe role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression
Dasgupta, N., Arnold, R., Equey, A., Gandhi, A., & Adams, P. D. (2024) · npj Aging · doi:10.1038/s41514-024-00172-2 · Cited by 86 · see citing works
Self-citationTargeting senescent cells to attenuate cardiovascular disease progression
Song, P., Zhao, Q., & Zou, M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101072 · Cited by 76 · see citing works
Therapeutic targeting of senescent cells in the CNS
Rießland, M., Ximerakis, M., Jarjour, A. A., Zhang, B., & Orr, M. E. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01033-z · Cited by 74 · see citing works
Giorgio, E. D., Paluvai, H., Dalla, E., Ranzino, L., Renzini, A., Moresi, V., Minisini, M., Picco, R., & Brancolini, C. (2021) · Genome biology · doi:10.1186/s13059-021-02340-z · Cited by 67 · see citing works
A hyper-quiescent chromatin state formed during aging is reversed by regeneration
Yang, N., Occean, J. R., Melters, D. P., Shi, C., Wang, L., Stransky, S., Doyle, M. E., Cui, C., Delannoy, M. R., Fan, J., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.04.005 · Cited by 71 · see citing works
Self-citationLiu, Y., Lomeli, I., & Kron, S. J. (2024) · Cells · doi:10.3390/cells13151281 · Cited by 72 · see citing works
Huang, Y., Mouttet, B., Warnatz, H.-J., Risch, T., Rietmann, F., Frommelt, F., Ngo, Q. A., Dobay, M. P., Marovca, B., Jenni, S., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.004 · Cited by 63 · see citing works
The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17
Chaves‐Moreira, D., Mitchell, M. A., Arruza, C., Rawat, P., Sidoli, S., Nameki, R. A., Reddy, J., Corona, R. I., Afeyan, L. K., Klein, I. A., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abm2496 · Cited by 57 · see citing works
Self-citationUsing Chemical Epigenetics to Target Cancer
Wimalasena, V. K., Wang, T., Sigua, L. H., Durbin, A. D., & Qi, J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.023 · Cited by 55 · see citing works
Wen, S., He, Y., Wang, L., Zhang, J., Quan, C., Niu, Y., & Huang, H. (2020) · Oncogene · doi:10.1038/s41388-020-01456-z · Cited by 54 · see citing works
Molecular Mechanisms of Autophagy Decline during Aging
Lim, S. H. Y., Hansen, M., & Kumsta, C. (2024) · Cells · doi:10.3390/cells13161364 · Cited by 53 · see citing works
The aging proteostasis decline: From nematode to human
Meller, A., & Shalgi, R. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112474 · Cited by 50 · see citing works
Senescent cells limit p53 activity via multiple mechanisms to remain viable
Sturmlechner, I., Sine, C. C., Jeganathan, K. B., Zhang, C., Velasco, R. O. F., Baker, D. J., Li, H., & van Deursen, J. M. (2022) · Nature Communications · doi:10.1038/s41467-022-31239-x · Cited by 45 · see citing works
Gao, X., Lai, Y., Luo, X., Peng, D., Li, Q., Zhou, H., Xue, Y., Guo, H., Zhao, J., Yang, H., et al. (2022) · Aging Cell · doi:10.1111/acel.13743 · Cited by 43 · see citing works
Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars
Martínez‐Zamudio, R. I., Stefa, A., de Freitas, J. A. N. L. F., Vasilopoulos, T., Simpson, M., Doré, G. R. G., Roux, P., Galan, M. A., Chokshi, R. J., Bischof, O., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100293 · Cited by 44 · see citing works
Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice
Li, X., Khan, I., Xia, W., Huang, G., Liu, L., Law, B. Y. K., Yin, L., Liao, W., Leong, W., Han, R., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105587 · Cited by 44 · see citing works
Integrated multi-omics approach revealed cellular senescence landscape
Song, Q., Hou, Y., Zhang, Y., Liu, J., Wang, Y., Fu, J., Zhang, C., Cao, M., Cui, Y., Zhang, X., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac885 · Cited by 42 · 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
Feigman, M. J., Moss, M. A., Chen, C., Cyrill, S. L., Ciccone, M. F., Trousdell, M. C., Yang, S.-T., Frey, W. D., Wilkinson, J. E., & dos Santos, C. O. (2020) · Nature Communications · doi:10.1038/s41467-020-16479-z · Cited by 38 · see citing works
Spurious intragenic transcription is a feature of mammalian cellular senescence and tissue aging
Sen, P., Donahue, G., Li, C. Y., Egervári, G., Yang, N., Lan, Y., Robertson, N., Shah, P. P., Kerkhoven, E., Schultz, D., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00384-3 · Cited by 37 · see citing works
Self-citationWang, C., Long, Q., Fu, Q., Xu, Q., Fu, D., Li, Y., Gao, L., Guo, J., Zhang, X., Lam, E. W. ‐., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02476-7 · Cited by 34 · see citing works
Ghosh, A. K. (2021) · Cells · doi:10.3390/cells10112839 · Cited by 33 · see citing works
Herman, A. B., Anerillas, C., Harris, S. C., Munk, R., Martindale, J. L., Yang, X., Mazan-Mamczarz, K., Zhang, Y., Heckenbach, I. J., Scheibye-Knudsen, M., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab538 · Cited by 31 · see citing works
Self-citationHistone modifications, DNA methylation, and the epigenetic code of alcohol use disorder
Bohnsack, J. P., & Pandey, S. C. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.08.005 · Cited by 32 · see citing works
A ride through the epigenetic landscape: aging reversal by reprogramming
Camillo, L. P. D. L., & Quinlan, R. B. A. (2021) · GeroScience · doi:10.1007/s11357-021-00358-6 · Cited by 30 · see citing works
Tieing together loose ends: telomere instability in cancer and aging
Borges, G. D. O., Criqui, M., & Harrington, L. A. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13299 · Cited by 31 · see citing works
Transcriptional changes of the aging lung
Jia, M., Garcia, P. A. A., Ovando-Ricárdez, J. A., Tabib, T., Bittar, H. E. T., Lafyatis, R., Mora, A. L., Benos, P. V., & Rojas, M. M. (2023) · Aging Cell · doi:10.1111/acel.13969 · Cited by 30 · see citing works
Epigenetic biomarkers in aging and longevity: Current and future application
Izadi, M., Sadri, N., Abdi, A., Serajian, S., Jalalei, D., & Tahmasebi, S. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122842 · Cited by 30 · see citing works
Wandering along the epigenetic timeline
Topart, C., Werner, E., & Arimondo, P. B. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00893-7 · Cited by 29 · see citing works
Feng, M., Xu, H., Zhou, W., & Pan, Y. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02615-2 · Cited by 29 · see citing works
Zhang, R.-K., Li, Y., Sun, F.-L., Zhou, Z.-H., Xie, Y.-X., Liu, W., Wang, W. J., Qiu, J.-G., Jiang, B., & Wang, L. (2024) · Environment International · doi:10.1016/j.envint.2024.109055 · Cited by 28 · see citing works
Epigenetic enzymes: A role in aging and prospects for pharmacological targeting
PASYUKOVA, E. G., Symonenko, A. V., Rybina, O. Y., & Vaiserman, A. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101312 · Cited by 27 · see citing works
Hu, D., Hu, Y., Zhan, T., Zheng, Y., Ran, P., Liu, X., Guo, Z., Wei, W., & Wang, S. (2019) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2019.111934 · Cited by 27 · see citing works
Grosse, L., & Bulavin, D. V. (2020) · Aging · doi:10.18632/aging.103492 · Cited by 27 · 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
Allegra, A., Caserta, S., Mirabile, G., & Gangemi, S. (2023) · Cells · doi:10.3390/cells12192392 · Cited by 29 · see citing works
Giorgio, E. D., Dalla, E., Tolotto, V., D’Este, F., Paluvai, H., Ranzino, L., & Brancolini, C. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae501 · Cited by 24 · see citing works
Riparini, G., Mackenzie, M. E., Naz, F., Brooks, S. R., Jiang, K., Deewan, A., Dulek, B., Islam, S., Ko, K. D., Tsai, W. L., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-01002-0 · Cited by 24 · see citing works
Senescence: An Identity Crisis Originating from Deep Within the Nucleus
Olan, I., & Narita, M. (2022) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-013537 · Cited by 23 · see citing works
Liao, R. J., Wu, Y., Qin, L., Jiang, Z., Gou, S., Zhou, L., Hong, Q., Li, Y., Shi, J., Yao, Y., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2023113448 · Cited by 23 · see citing works
Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging
Smith, N., Shirazi, S., Cakouros, D., & Gronthos, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076499 · Cited by 23 · see citing works
Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition
Shendy, N. A. M., Bikowitz, M. J., Sigua, L. H., Zhang, Y., Mercier, A. L., Khashana, Y., Nance, S., Liu, Q., Delahunty, I. M., Robinson, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47102-0 · Cited by 21 · see citing works
Therapeutic strategies targeting cellular senescence for cancer and other diseases
Wang, X., Fukumoto, T., & Noma, K.-I. (2024) · The Journal of Biochemistry · doi:10.1093/jb/mvae015 · Cited by 21 · see citing works
Gómez‐Pinilla, F., & Thapak, P. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.04.237 · Cited by 21 · see citing works
Balamurli, G., Liew, A. Q. X., Tee, W., & Pervaiz, S. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103441 · Cited by 22 · see citing works
Ansari, M. S. Z., Stagni, V., Iuzzolino, A., Rotili, D., Mai, A., Bufalo, D. D., Lavia, P., Degrassi, F., & Trisciuoglio, D. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00524-8 · Cited by 20 · see citing works
Chen, L., Liao, F., Wu, J., Wang, Z., Jiang, Z., Zhang, C., Luo, P., Ma, L., Gong, Q., Wang, Y., et al. (2021) · Aging Cell · doi:10.1111/acel.13370 · Cited by 19 · see citing works
Taking the road less traveled – the therapeutic potential of CBP/β-catenin antagonists
Kahn, M. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1992386 · Cited by 19 · see citing works
Tang, C., Chen, H., Jiang, L., & Liu, L. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9018811 · Cited by 19 · see citing works
Liu, J., Zheng, R., Zhang, Y., Jia, S., He, Y., & Liu, J. (2023) · Cancers · doi:10.3390/cancers15092640 · Cited by 19 · see citing works
Frey, Y., Haj, M., Ziv, Y., Elkon, R., & Shiloh, Y. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1257 · Cited by 18 · see citing works
Turano, P. S., Akbulut, E., Dewald, H. K., Vasilopoulos, T., Fitzgerald-Bocarsly, P., Herbig, U., & Martínez-Zamudio, R. I. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116795 · Cited by 16 · see citing works
Senescence in cancer: Hallmarks, paradoxes, and therapeutic promise
Hinterleitner, C., Goldberg, H. V., McHugh, D., Barthet, V. J. A., Filliol, A. A., & Lowe, S. W. (2026) · Cell · doi:10.1016/j.cell.2026.03.005 · Cited by 18 · see citing works
Molecular basis for SOX2-dependent regulation of super-enhancer activity
Yoo, W., Song, Y. W., Kim, J., Ahn, J., Kim, J., Shin, Y., Ryu, J., & Kim, K. K. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad908 · Cited by 16 · see citing works
Ye, C., Cheng, Y. H., Qian, X., Zhong, B., Ma, J., & Guo, H. (2024) · Biochemical Genetics · doi:10.1007/s10528-024-10704-w · Cited by 16 · see citing works
Agosto, L. M., Mallory, M. J., Ferretti, M., Blake, D., Krick, K. S., Gazzara, M. R., Garcia, B. A., & Lynch, K. W. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112273 · Cited by 14 · see citing works
Self-citationQiu, X., Lin, J., Liang, B., Chen, Y., Liu, G., & Zheng, J. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.636934 · Cited by 14 · see citing works
Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma
Wei, E., Mitanoska, A., O'Brien, Q., Porter, K., Molina, M., Ahsan, H., Jung, U., Mills, L. J., Kyba, M., & Bosnakovski, D. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02115-7 · Cited by 13 · see citing works
Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence
Daigh, L. H., Saha, D., Rosenthal, D. L., Ferrick, K. R., & Meyer, T. (2024) · Nature Communications · doi:10.1038/s41467-024-52820-6 · Cited by 14 · see citing works
Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target
Yücel, A. D., & Gladyshev, V. N. (2026) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-026-00958-0 · Cited by 12 · see citing works
Increased chromatin accessibility underpins senescence
Lopes‐Paciencia, S., & Ferbeyre, G. (2025) · FEBS Journal · doi:10.1111/febs.70136 · Cited by 14 · see citing works
Breaking the aging epigenetic barrier
Sikder, S., Arunkumar, G., Melters, D. P., & Dalal, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.943519 · Cited by 12 · see citing works
Cellular senescence and tumor promotion: Role of the Unfolded Protein Response.
Pluquet, O., & Abbadie, C. (2021) · Advances in Cancer Research · doi:10.1016/bs.acr.2021.01.001 · Cited by 8 · see citing works
He, Z., Peng, H., Gao, M., Liang, G.-B., Zeng, M., & Zhang, X. (2021) · Mediators of Inflammation · doi:10.1155/2021/5599364 · Cited by 12 · see citing works
Intracellular signaling modules linking DNA damage to secretome changes in senescent melanoma cells
Chavanet, A., Hill, K. R., Jiménez-Andrade, Y., Choo, M., White, K., & Park, J. M. (2020) · Melanoma Research · doi:10.1097/cmr.0000000000000671 · Cited by 11 · see citing works
A senescence restriction point acting on chromatin integrates oncogenic signals
Lopes‐Paciencia, S., Bourdeau, V., Rowell, M., Amirimehr, D., Guillon, J., Kalegari, P., Barua, A., Trinh, V. Q., Azzi, F., Turcotte, S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114044 · Cited by 11 · see citing works
Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review
Gioukaki, C., Georgiou, A., Gkaralea, L. E., Κroupis, C., Lazaris, A. C., Alamanis, C., & Thomopoulou, G. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411299 · Cited by 11 · see citing works
Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence
Scanlan, R.-L., Pease, L., O’Keefe, H., Guimera, A. M., Rasmussen, L. J., Wordsworth, J., & Shanley, D. P. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1448543 · Cited by 11 · see citing works
Interrogating the regulatory epigenome of cellular senescence
Thanos, D.-F., Ntintas, O. A., Athanasiadis, E. I., Papaspyropoulos, A., Petty, R., & Gorgoulis, V. G. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05848-w · Cited by 10 · see citing works
Tuz-Sasik, M. U., Karoglu-Eravsar, E. T., Kinali, M., Ergul, A. A., & Adams, M. M. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.04.003 · Cited by 10 · see citing works
Zumerle, S., & Alimonti, A. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0540-x · Cited by 10 · see citing works
Hettler, F., Schreck, C., Marquez, S. R., Engleitner, T., Vilne, B., Landspersky, T., Weidner, H., Hausinger, R. I., Mishra, R., Oellinger, R., et al. (2022) · Haematologica · doi:10.3324/haematol.2022.280760 · Cited by 9 · see citing works
Differential Kat3 Usage Orchestrates the Integration of Cellular Metabolism with Differentiation
Hu, X., Ono, M., Chimge, N., Chosa, K., Nguyen, C., Melendez, E., Lou, C., Lim, P. P., Termini, J. S., Lai, K. K. Y., et al. (2021) · Cancers · doi:10.3390/cancers13235884 · Cited by 9 · see citing works
PAX8 orchestrates an angiogenic program through interaction with SOX17Preprint
Chaves‐Moreira, D., Mitchell, M. A., Arruza, C., Rawat, P., Sidoli, S., Nameki, R. A., Reddy, J., Corona, R. I., Ma, S., Winterhoff, B. J. N., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.09.290387 · Cited by 9 · see citing works
Self-citationRole of transcriptional cofactors in cardiovascular diseases
Mao, S., Song, C., Huang, H., Nie, Y., Ding, K., Cui, J. G., Tian, J., & Tang, H. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149757 · Cited by 8 · see citing works
- Authors
- Sen, P., Lan, Y., Li, C. Y., Sidoli, S., Donahue, G., Dou, Z., Frederick, B., Chen, Q., Luense, L. J., Garcia, B. A., Dang, W., Johnson, F. B., Adams, P. D., Schultz, D. C., & Berger, S. L.
- Affiliations
- University of Pennsylvania (US)
- Baylor College of Medicine (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Berger, Shelley L.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 73
- Issue
- 4
- Pages
- 684-698.e8
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6688479
- OpenAlex
- W2913142344
- Cited by
- 164
- References
- 54
- Citations by year
- 2026: 27 · 2025: 13 · 2024: 26 · 2023: 24 · 2022: 20 · 2021: 25 · 2020: 23 · 2019: 6
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P01AG031862, CA196539, GM110174, AI118891)
- CPRIT (R1306)
- Ted Nash Long Life Foundation
- American Heart Association (15POST21230000)
- AFAR (DIAMOND 17113)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- 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
- Keywords
- P300, cellular senescence, super-enhancers, histone acetyltransferase, histone acetylation, replicative senescence, epigenetic regulation, non-coding genome, senescence-associated gene expression, CBP, aging, age-related diseases, therapeutic target
- MeSH terms
- p300-CBP-Associated Factor, Acetylation, Chromatin, Fibroblasts, Histones, Humans, Protein Processing, Post-Translational, Time Factors, Transcription, Genetic, Signal Transduction, Cellular Senescence, RNA Interference, RNA, Small Interfering, Chromatin Assembly and Disassembly, Cell Proliferation, p300-CBP Transcription Factors, HEK293 Cells, High-Throughput Nucleotide Sequencing, Epigenetic Repression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
