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Research: Polycomb misregulation in enterocytes drives tissue decline in the aging Drosophila intestine
- Sarah M. Leichter,
- Kami Ahmad,
- and Steven Henikoff
Genome Res. January 2026 36: 102-114; Published in Advance November 17, 2025, doi:10.1101/gr.281058.125
...cells to re-enter the cell cycle partially restores a youthful H3K27me3 landscape, suggesting that DNA replication may rejuvenate chromatin structure (Yang et al. 2023). However, even mitotically active somatic stem cells display age-related increases in Polycomb repression: Aged Drosophila intestinal...
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Research: Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice
- Leandros Boukas,
- Teresa Romeo Luperchio,
- Afrooz Razi,
- Kasper D. Hansen,
- and Hans T. Bjornsson
Genome Res. May 2024 34: 696-710; Published in Advance May 3, 2024, doi:10.1101/gr.278416.123
..., answering this question is important for understanding the potential of DNA methylation–based episignatures (Aref-Eshghi et al. 2021; Levy et al. 2022a) to shed light on the pathogenesis of the disorders. Although these episignatures are almost exclusively derived from whole blood, there is increasing...
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Research: Widespread formation of double-stranded RNAs in testis
- Andreas Werner,
- James E. Clark,
- Calum Samaranayake,
- John Casement,
- Hany S. Zinad,
- Shaymaa Sadeq,
- Surar Al-Hashimi,
- Martin Smith,
- Noora Kotaja,
- and John S. Mattick
Genome Res. July 2021 31: 1174-1186; Published in Advance June 22, 2021, doi:10.1101/gr.265603.120
...as a result of widespread NAT expression but also of pervasive transcription from repetitive regions of the and bidirectional transcription of mitochondrial DNA (Kim et al. 2019). The formation of endogenous dsRNA, however, conflicts with the cell's defense system against viruses, which is geared to recognize...
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Resource: Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
- Bérénice A. Benayoun,
- Elizabeth A. Pollina,
- Param Priya Singh,
- Salah Mahmoudi,
- Itamar Harel,
- Kerriann M. Casey,
- Ben W. Dulken,
- Anshul Kundaje,
- and Anne Brunet
Genome Res. April 2019 29: 697-709; Published in Advance March 11, 2019, doi:10.1101/gr.240093.118
...(e.g., age-related changes in H3K4me3 breadth), (2) “static”—describing the youthful state of the chromatin or DNA sequence at the gene (e.g., H3K27ac in young tissue), or (3) both (Fig. 3A; Supplemental Fig. S3A). Because absolute gene expression levels can influence the ability to call differential...
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Research: Age-related epigenetic drift in the pathogenesis of MDS and AML
- Shinji Maegawa,
- Sheryl M. Gough,
- Naoko Watanabe-Okochi,
- Yue Lu,
- Nianxiang Zhang,
- Ryan J. Castoro,
- Marcos R.H. Estecio,
- Jaroslav Jelinek,
- Shoudan Liang,
- Toshio Kitamura,
- Peter D. Aplan,
- and Jean-Pierre J. Issa
Genome Res. April 2014 24: 580-591; Published in Advance January 10, 2014, doi:10.1101/gr.157529.113
...also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA...
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Method: A pooling-based approach to mapping genetic variants associated with DNA methylation
- Irene M. Kaplow,
- Julia L. MacIsaac,
- Sarah M. Mah,
- Lisa M. McEwen,
- Michael S. Kobor,
- and Hunter B. Fraser
Genome Res. June 2015 25: 907-917; Published in Advance April 24, 2015, doi:10.1101/gr.183749.114
...for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any...
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Resource: A DNA methylation fingerprint of 1628 human samples
- Agustin F. Fernandez,
- Yassen Assenov,
- Jose Ignacio Martin-Subero,
- Balazs Balint,
- Reiner Siebert,
- Hiroaki Taniguchi,
- Hiroyuki Yamamoto,
- Manuel Hidalgo,
- Aik-Choon Tan,
- Oliver Galm,
- Isidre Ferrer,
- Montse Sanchez-Cespedes,
- Alberto Villanueva,
- Javier Carmona,
- Jose V. Sanchez-Mut,
- Maria Berdasco,
- Victor Moreno,
- Gabriel Capella,
- David Monk,
- Esteban Ballestar,
- Santiago Ropero,
- Ramon Martinez,
- Marta Sanchez-Carbayo,
- Felipe Prosper,
- Xabier Agirre,
- Mario F. Fraga,
- Osvaldo Graña,
- Luis Perez-Jurado,
- Jaume Mora,
- Susana Puig,
- Jaime Prat,
- Lina Badimon,
- Annibale A. Puca,
- Stephen J. Meltzer,
- Thomas Lengauer,
- John Bridgewater,
- Christoph Bock,
- and Manel Esteller
Genome Res. February 2012 22: 407-419; Published in Advance May 25, 2011, doi:10.1101/gr.119867.110
...with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1628 human samples in which we interrogated 1505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around...
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Research: DNA methylation contributes to natural human variation
- Holger Heyn,
- Sebastian Moran,
- Irene Hernando-Herraez,
- Sergi Sayols,
- Antonio Gomez,
- Juan Sandoval,
- Dave Monk,
- Kenichiro Hata,
- Tomas Marques-Bonet,
- Liewei Wang,
- and Manel Esteller
Genome Res. September 2013 23: 1363-1372; Published in Advance August 1, 2013, doi:10.1101/gr.154187.112
...of Physiological Sciences II, School of Medicine, University of Barcelona, 08036 Barcelona, Catalonia, Spain ↵ 7 These authors contributed equally to this work. Abstract DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known...
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Resource: Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging
- Jacob C. Kimmel,
- Lolita Penland,
- Nimrod D. Rubinstein,
- David G. Hendrickson,
- David R. Kelley,
- and Adam Z. Rosenthal
Genome Res. December 2019 29: 2088-2103; Published in Advance November 21, 2019, doi:10.1101/gr.253880.119
...and cells (Drigo et al. 2019). Studies of DNA methylation patterns with aging also suggest that different tissues age in unique ways (Horvath 2013). However, the cellular origins of aging phenotypes within a tissue remain largely unknown (Rodwell et al. 2004; O'Brown et al. 2015; Benayoun et al. 2019...
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Research: Ribosomal DNA harbors an evolutionarily conserved clock of biological aging
- Meng Wang and
- Bernardo Lemos
Genome Res. March 2019 29: 325-333; Published in Advance February 14, 2019, doi:10.1101/gr.241745.118
...in tissue types and strains (Spearman's ρ ≥ 0.24, P ≤ 6.38 × 10−9) (Supplemental Fig. S4).View larger version: In this window In a new window Figure 1. Ribosomal DNA methylation is strongly associated with age. (A) Age-associated hypermethylation of rDNA CpGs in mice. Spearman's correlation coefficients...

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