Chromatin remodeling in the aging genome of Drosophila
Open accessAbstract
Summary: Chromatin structure affects the accessibility of DNA to transcription, repair, and replication. Changes in chromatin structure occur during development, but less is known about changes during aging. We examined the state of chromatin structure and its effect on gene expression during aging in Drosophila at the whole genome and cellular level using whole‐genome tiling microarrays of activation and repressive chromatin marks, whole‐genome transcriptional microarrays and single‐cell immunohistochemistry. We found dramatic reorganization of chromosomal regions with age. Mapping of H3K9me3 and HP1 signals to fly chromosomes reveals in young flies the expected high enrichment in the pericentric regions, the 4th chromosome, and islands of facultative heterochromatin dispersed throughout the genome. With age, there is a striking reduction in this enrichment resulting in a nearly equivalent level of H3K9me3 and HP1 in the pericentric regions, the 4th chromosome, facultative heterochromatin, and euchromatin. These extensive changes in repressive chromatin marks are associated with alterations in age‐related gene expression. Large‐scale changes in repressive marks with age are further substantiated by single‐cell immunohistochemistry that shows changes in nuclear distribution of H3K9me3 and HP1 marks with age. Such epigenetic changes are expected to directly or indirectly impinge upon important cellular functions such as gene expression, DNA repair, and DNA replication. The combination of genome‐wide approaches such as whole‐genome chromatin immunoprecipitation and transcriptional studies in conjunction with single‐cell immunohistochemistry as shown here provide a first step toward defining how changes in chromatin may contribute to the process of aging in metazoans.
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?
In Drosophila, H3K9me3 and HP1 decline with age in pericentric regions and islands of heterochromatin.
“In Drosophila, H3K9me3 and HP1 decline with age in pericentric regions and islands of heterochromatin58.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [58]
The Results (‘Repressive marks change with age’) report reduced enrichment of H3K9me3 and HP1 in pericentric regions and islands of facultative heterochromatin relative to euchromatin. The Discussion cautions that ChIP-chip cannot establish whether either mark actually declines in those regions with age; increased marking in euchromatin could produce the same pattern. The unqualified claim of a decline therefore overstates the finding. (LLM, conf=0.90)
Experimental — accuracy not yet measuredRetrotransposons become reactivated in cell senescence and with age in both mammals and Drosophila.
“Retrotransposons become reactivated in cell senescence and with age in both mammals and Drosophila58, 60, 66, 68.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [58]
The Discussion raises the possibility of age-related changes in transposon RNA in Drosophila, but says the study could not detect them with its transcriptional microarrays. It does not establish retrotransposon reactivation, and it provides no finding about mammalian cell senescence. (LLM, conf=0.85)
Experimental — accuracy not yet measuredH3K4me3 deposition changes with age in murine hematopoietic stem cells, Drosophila, and cellular senescence in human fibroblasts.
“H3K4me3, a mark associated with active transcription, has also been implicated in longevity, and its deposition changes with age in murine hematopoietic stem cells and in Drosophila (Sun et al., 2014; Wood et al., 2010) and cellular senescence in human fibroblasts (Shah et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Wood et al., 2010
Age-related H3K4me2/3 deposition changes may alter KDM5/RBR-2 activation of key mitochondrial genes.
“changes in H3K4me2/3 deposition with age (Sun et al., 2014; Wood et al., 2010) may alter the ability of the H3K4me2/3 demethylase KDM5/RBR-2 to activate the transcription of key mitochondrial genes (Liu and Secombe, 2015).”
From The Aging Epigenome (2016) · cites this paper as Wood et al., 2010
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 tutorial on hidden Markov models and selected applications in speech recognition
Rabiner, L. R. (1989) · Proceedings of the IEEE · doi:10.1109/5.18626 · Cited by 22,743 · see citing works
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · 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
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503 · see citing works
The complex language of chromatin regulation during transcription
Berger, S. L. (2007) · Nature · doi:10.1038/nature05915 · Cited by 2,768 · see citing works
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,238 · see citing works
ChIP–seq: advantages and challenges of a maturing technology
Park, P. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2641 · Cited by 2,217 · see citing works
A Model-Based Background Adjustment for Oligonucleotide Expression Arrays
Wu, Z. J., Irizarry, R. A., Gentleman, R. C., Martínez-Murillo, F., & Spencer, F. A. (2004) · Journal of the American Statistical Association · doi:10.1198/016214504000000683 · Cited by 1,717 · see citing works
Grewal, S. I. S., & Jia, S. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2008 · Cited by 1,263 · see citing works
A 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
Histone modification levels are predictive for gene expression
Karlić, R., Chung, H., Lasserre, J., Vlahoviček, K., & Vingron, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909344107 · Cited by 794 · see citing works
RNA polymerase is poised for activation across the genome
Muse, G. W., Gilchrist, D. A., Nechaev, S., Shah, R., Parker, J. S., Grissom, S. F., Zeitlinger, J., & Adelman, K. (2007) · Nature Genetics · doi:10.1038/ng.2007.21 · Cited by 762 · see citing works
Histone lysine methylation: a signature for chromatin function
Sims, R. J., Nishioka, K., & Reinberg, D. (2003) · Trends in Genetics · doi:10.1016/j.tig.2003.09.007 · Cited by 684 · 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
Histone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667 · see citing works
Expression switching in the stevor and Pfmc‐2TM superfamilies in Plasmodium falciparum
Lavazec, C., Sanyal, S., & Templeton, T. J. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05767.x · Cited by 659 · see citing works
Genomic characterization reveals a simple histone H4 acetylation code
Dion, M. F., Altschuler, S. J., Wu, L. F., & Rando, O. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500136102 · Cited by 395 · see citing works
H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability
Peng, J. C., & Karpen, G. H. (2007) · Nature Cell Biology · doi:10.1038/ncb1514 · Cited by 375 · see citing works
Genome-wide approaches to studying chromatin modifications
Schones, D. E., & Zhao, K. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2270 · Cited by 370 · see citing works
Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae
Smeal, T., Claus, J., Kennedy, B., Cole, F., & Guarente, L. (1996) · Cell · doi:10.1016/s0092-8674(00)81038-7 · Cited by 308 · see citing works
Su(var) genes regulate the balance between euchromatin and heterochromatin in DrosophilaPreprint
Ebert, A., Schotta, G., Lein, S., Kubicek, S., Krauß, V., Jenuwein, T., & Reuter, G. (2004) · Genes & Development · doi:10.1101/gad.323004 · Cited by 277 · see citing works
Kyes, S., Christodoulou, Z., Pinches, R. A., Kriek, N., Horrocks, P., & Newbold, C. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05587.x · Cited by 257 · see citing works
Chromosomal Distribution of PcG Proteins during Drosophila Development
Negre, N. N., Hennetin, J., Sun, L. V., Lavrov, S. A., Bellis, M., White, K. P., & Cavalli, G. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040170 · Cited by 246 · see citing works
Histone modification and the control of heterochromatic gene silencing in Drosophila
Ebert, A., Lein, S., Schotta, G., & Reuter, G. (2006) · Chromosome Research · doi:10.1007/s10577-006-1066-1 · Cited by 209 · see citing works
Heterochromatin: silence is golden
Elgin, S. C. R., & Grewal, S. I. S. (2003) · Current Biology · doi:10.1016/j.cub.2003.11.006 · Cited by 199 · see citing works
Discovery and Annotation of Functional Chromatin Signatures in the Human Genome
Hon, G. C., Wang, W., & Ren, B. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000566 · Cited by 169 · see citing works
Aging by epigenetics—A consequence of chromatin damage?
Sedivy, J. M., Gowrishankar, B., & Adams, P. D. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.023 · Cited by 153 · see citing works
Chromatin poises miRNA- and protein-coding genes for expressionPreprint
Barski, A., Jothi, R., Cuddapah, S., Cui, K., Roh, T., Schones, D. E., & Zhao, K. (2009) · Genome Research · doi:10.1101/gr.090951.109 · Cited by 147 · see citing works
Yasuhara, J. C., & Wakimoto, B. T. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0040016 · Cited by 94 · see citing works
Effect of Replicative Age on Transcriptional Silencing Near Telomeres inSaccharomyces cerevisiae
Kim, S., Villeponteau, B., & Jazwinski, S. M. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0240 · Cited by 73 · see citing works
Epigenetics meets next-generation sequencing
Park, P. J. (2008) · Epigenetics · doi:10.4161/epi.3.6.7249 · Cited by 43 · see citing works
Spreading of silent chromatin: inaction at a distance
Talbert, P. B., & Henikoff, S. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1920
Flagged first, then by citations
Cited by
Sorted by citations
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
Pal, S., & Tyler, J. K. (2016) · Science Advances · doi:10.1126/sciadv.1600584 · Cited by 860 · see citing works
Lysosome-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
Booth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499 · see citing works
The role of retrotransposable elements in ageing and age-associated diseases
Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyö, D., Boeke, J. D., Linker, S. B., Gage, F. H., Kreiling, J. A., Petrashen, A. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03542-y · Cited by 457 · see citing works
Self-citationAging and epigenetic drift: a vicious cycle
Issa, J.-P. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69735 · Cited by 419 · see citing works
Epigenetic changes during aging and their reprogramming potential
Kane, A. E., & Sinclair, D. A. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1570075 · Cited by 283 · see citing works
Wood, J. G., Jones, B. C., Jiang, N., Chang, C., Hosier, S., Wickremesinghe, P., Garcia, M., Hartnett, D. A., Burhenn, L., Neretti, N., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604621113 · Cited by 214 · see citing works
Self-citationGriñán-Ferré, C., Bellver-Sanchis, A., Izquierdo, V., Corpas, R., Roig-Soriano, J., Chillón, M., Andres-Lacueva, C., Somogyvári, M., Sőti, C., Sanfeliu, C., et al. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101271 · Cited by 208 · see citing works
Histone methylation makes its mark on longevity
Han, S., & Brunet, A. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.11.001 · Cited by 204 · see citing works
Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS
Krug, L., Chatterjee, N., Borges-Monroy, R., Hearn, S., Liao, W.-W., Morrill, K., Prazak, L., Rozhkov, N., Theodorou, D., Hammell, M., et al. (2017) · PLOS Genetics · doi:10.1371/journal.pgen.1006635 · Cited by 201 · see citing works
vel Szic, K. S., Declerck, K., Vidaković, M., & Vanden Berghe, W. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0068-2 · Cited by 192 · see citing works
Aging and reprogramming: a two-way street
Mahmoudi, S., & Brunet, A. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.10.004 · Cited by 171 · see citing works
Age‐associated increase in heterochromatic marks in murine and primate tissues
Kreiling, J. A., Tamamori‐Adachi, M., Sexton, A. N., Jeyapalan, J. C., Munoz‐Najar, U., Peterson, A. L., Manivannan, J., Rogers, E. S., Pchelintsev, N. A., Adams, P. D., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00666.x · Cited by 152 · see citing works
The Information Theory of Aging
Lu, Y. R., Tian, X., & Sinclair, D. A. (2023) · Nature Aging · doi:10.1038/s43587-023-00527-6 · Cited by 141 · see citing works
Chen, H., Zheng, X., Xiao, D., & Zheng, Y. (2016) · Aging Cell · doi:10.1111/acel.12465 · Cited by 107 · see citing works
HDAC inhibitors: A new promising drug class in anti-aging research
Pasyukova, E. G., & Vaiserman, A. M. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.008 · Cited by 99 · see citing works
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1978-z · Cited by 99 · see citing works
Histone methylation and aging: Lessons learned from model systems
McCauley, B. S., & Dang, W. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.05.008 · Cited by 93 · see citing works
Involvement of Redox State in the Aging of <i>Drosophila melanogaster</i>
Orr, W. C., Radyuk, S. N., & Sohal, R. S. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5002 · Cited by 55 · see citing works
Jiang, N., Du, G., Tobias, E., Wood, J. G., Whitaker, R., Neretti, N., & Helfand, S. L. (2013) · Aging · doi:10.18632/aging.100614 · Cited by 54 · see citing works
Self-citation
- Authors
- Wood, J. G., Hillenmeyer, S., Lawrence, C., Chang, C., Hosier, S., Lightfoot, W., Mukherjee, E., Jiang, N., Schorl, C., Brodsky, A. S., Neretti, N., & Helfand, S. L.
- Affiliations
- Brown University (US)
- Corresponding author
- Neretti, Nicola
- Helfand, Stephen L.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-10-21
- Volume
- 9
- Issue
- 6
- Pages
- 971-978
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2980570
- OpenAlex
- W1586705837
- Cited by
- 192
- References
- 32
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 7 · 2023: 20 · 2022: 10 · 2021: 26 · 2020: 13 · 2019: 17 · 2018: 12 · 2017: 9 · 2016: 12 · 2015: 14 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- National Institute on Aging (R01AG025277, K25AG028753, RF1AG024353, AG16667, AG24353, AG25277, R01AG024353, R01AG016667, R37AG016667, AG028753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin remodeling, aging, Drosophila, H3K9me3, HP1, facultative heterochromatin, age-related gene expression, epigenetic modifications, pericentromeric heterochromatin, chromosomal rearrangements
- MeSH terms
- Aging, Animals, DNA Replication, Drosophila, Immunohistochemistry, Genome, Genes, Insect, Drosophila Proteins, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation
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
