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Research: An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells
- Veronica Astro,
- Kelly Yojanna Cardona-Londoño,
- Lorena Viridiana Cortés-Medina,
- Rawan Alghamdi,
- Gustavo Ramírez-Calderón,
- Fotios Kefalas,
- Jair Dilmé-Capó,
- Santiago Radío,
- and Antonio Adamo
Genome Res. July 2025 35: 1503-1517; Published in Advance June 10, 2025, doi:10.1101/gr.279716.124
...convergence underscores potential commonalities in the molecular pathways underpinning the pathophysiology of male sex-chromosome aneuploidies. Finally, through -wide DNA methylation profiling of JS iPSCs, we demonstrate that a supernumerary Y Chromosome only minimally impacts the methylation status of 47,XYY...
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Research: DNA methylation epitypes highlight underlying developmental and disease pathways in acute myeloid leukemia
- Brian Giacopelli,
- Min Wang,
- Ada Cleary,
- Yue-Zhong Wu,
- Anna Reister Schultz,
- Maximilian Schmutz,
- James S. Blachly,
- Ann-Kathrin Eisfeld,
- Bethany Mundy-Bosse,
- Sebastian Vosberg,
- Philipp A. Greif,
- Rainer Claus,
- Lars Bullinger,
- Ramiro Garzon,
- Kevin R. Coombes,
- Clara D. Bloomfield,
- Brian J. Druker,
- Jeffrey W. Tyner,
- John C. Byrd,
- and Christopher C. Oakes
Genome Res. May 2021 31: 747-761; Published in Advance March 11, 2021, doi:10.1101/gr.269233.120
...-cell-like phenotypes. Detailed analyses of DNA methylation patterns identified unique patterns of aberrant hyper- and hypomethylation among epitypes, with variable involvement of transcription factors influencing promoter, enhancer, and repressed regions. Patients in epitypes with stem-cell-like methylation features...
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Method: Single-cell methylation sequencing data reveal succinct metastatic migration histories and tumor progression models
- Yuelin Liu,
- Xuan Cindy Li,
- Farid Rashidi Mehrabadi,
- Alejandro A. Schäffer,
- Drew Pratt,
- David R. Crawford,
- Salem Malikić,
- Erin K. Molloy,
- Vishaka Gopalan,
- Stephen M. Mount,
- Eytan Ruppin,
- Kenneth D. Aldape,
- and S. Cenk Sahinalp
Genome Res. July 2023 33: 1089-1100; Published in Advance June 14, 2023, doi:10.1101/gr.277608.122
...in the data sets, which calls for data imputation or aggregation; on the other hand, tumor lineage inference using CNAs called from single-cell sequencing data often involves ambiguities in the determination of chromosomal breakpoints that may mislead the conclusion. DNA methylation, the addition of a methyl...
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Research: E4F1 and ZNF148 are transcriptional activators of the −57A > C and wild-type TERT promoter
- Boon Haow Chua,
- Nurkaiyisah Zaal Anuar,
- Laure Ferry,
- Cecilia Domrane,
- Anna Wittek,
- Vineeth T. Mukundan,
- Sudhakar Jha,
- Falk Butter,
- Daniel G. Tenen,
- Pierre-Antoine Defossez,
- and Dennis Kappei
Genome Res. November 2023 33: 1893-1905; Published in Advance November 2, 2023, doi:10.1101/gr.277724.123
...with hypermethylation around the TPM sites in cancer cells and hypomethylation in noncancerous primary cells (Dessain et al. 2000; Renaud et al. 2007; Stern et al. 2017), we next tested whether the DNA methylation pattern is altered between cell lines with different TPM status. To this end, we conducted pyrosequencing...
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Research: A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes
- Lei Zhang,
- Anshun He,
- Bohan Chen,
- Jinfang Bi,
- Jun Chen,
- Dianhao Guo,
- Yuyang Qian,
- Wenbin Wang,
- Tengfei Shi,
- Zhongfang Zhao,
- Jiandang Shi,
- Woojin An,
- Frank Attenello,
- and Wange Lu
Genome Res. February 2020 30: 155-163; Published in Advance January 17, 2020, doi:10.1101/gr.251058.119
...prognosis.Glioma resistance to TMZ is associated with multiple factors. Some report that high expression of O-6-methylguanine-DNA methyltransferase (MGMT) is related to robust TMZ resistance (Kitange et al. 2009; Wick et al. 2014). In addition, factors such as P4HB (Sun et al. 2013), ALDH1A1 (Schäfer et al...
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Research: Critical threshold levels of DNA methyltransferase 1 are required to maintain DNA methylation across the genome in human cancer cells
- Yi Cai,
- Hsing-Chen Tsai,
- Ray-Whay Chiu Yen,
- Yang W. Zhang,
- Xiangqian Kong,
- Wei Wang,
- Limin Xia,
- and Stephen B. Baylin
Genome Res. April 2017 27: 533-544; Published in Advance February 23, 2017, doi:10.1101/gr.208108.116
...with or without methylated gene promoters (Fig. 4A,B; Supplemental Fig. S6A). Importantly, in genes with high basal DNA methylation in both promoter and gene body regions, promoter methylation plays a more dominant role for transcriptional regulation, since genes with hypermethylated promoters have up...
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Research: A heterozygous IDH1^R132H/WT mutation induces genome-wide alterations in DNA methylation
- Christopher G. Duncan,
- Benjamin G. Barwick,
- Genglin Jin,
- Carlo Rago,
- Priya Kapoor-Vazirani,
- Doris R. Powell,
- Jen-Tsan Chi,
- Darell D. Bigner,
- Paula M. Vertino,
- and Hai Yan
Genome Res. December 2012 22: 2339-2355; Published in Advance August 16, 2012, doi:10.1101/gr.132738.111
...dehydrogenases IDH1 and IDH2 occur frequently in gliomas, acute myeloid leukemias, and chondromas, and display robust association with specific DNA hypermethylation signatures. Here we show that heterozygous expression of the IDH1R132H allele is sufficient to induce the -wide alterations in DNA methylation...
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Research: Genome-scale analysis of aberrant DNA methylation in colorectal cancer
- Toshinori Hinoue,
- Daniel J. Weisenberger,
- Christopher P.E. Lange,
- Hui Shen,
- Hyang-Min Byun,
- David Van Den Berg,
- Simeen Malik,
- Fei Pan,
- Houtan Noushmehr,
- Cornelis M. van Dijk,
- Rob A.E.M. Tollenaar,
- and Peter W. Laird
Genome Res. February 2012 22: 271-282; Published in Advance June 9, 2011, doi:10.1101/gr.117523.110
...by distinct genetic and epigenetic alterations. Here we performed comprehensive -scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic...
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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
...transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG-island hypermethylation and a loss of CpG methylation in non-CpG-island promoters. Although...
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Resource: Dynamic DNA methylation across diverse human cell lines and tissues
- Katherine E. Varley,
- Jason Gertz,
- Kevin M. Bowling,
- Stephanie L. Parker,
- Timothy E. Reddy,
- Florencia Pauli-Behn,
- Marie K. Cross,
- Brian A. Williams,
- John A. Stamatoyannopoulos,
- Gregory E. Crawford,
- Devin M. Absher,
- Barbara J. Wold,
- and Richard M. Myers
Genome Res. March 2013 23: 555-567; Published in Advance January 16, 2013, doi:10.1101/gr.147942.112
...for integrated analysis of DNA methylation, gene expression, transcription factor binding, and chromatin modifications. We demonstrate that comparisons of methylation profiles across the diverse collection of samples in this study can be used to investigate cancer-associated methylation defects, cell...

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