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Research: Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
- Kevin Moyung,
- Yulong Li,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. January 2026 36: 115-128; Published in Advance December 9, 2025, doi:10.1101/gr.279637.124
...with the up- and downregulation of genes and use these signatures to reveal regulatory mechanisms previously unexplored in expression-based studies. Finally, we demonstrate that chromatin features are predictive of transcriptional activity, and we leverage these features to reconstruct chromatin...
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Research: Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations
- Irene Mei,
- Susanne Nichterwitz,
- Melanie Leboeuf,
- Jik Nijssen,
- Isadora Lenoel,
- Dirk Repsilber,
- Christian S. Lobsiger,
- and Eva Hedlund
Genome Res. September 2025 35: 1975-1991; Published in Advance July 17, 2025, doi:10.1101/gr.279501.124
...no indication at the transcriptome level that CN3/4 MNs would have a better capacity to degrade proteins than spinal MNs in wild-type or SOD1G93A mice (Supplemental Fig. S2G), but this does not exclude translational or post-translational regulation of proteasome activity or differences in mESC-derived versus...
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Research: Androgen receptor–mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells
- Johannes Hiltunen,
- Laura Helminen,
- Niina Aaltonen,
- Kaisa-Mari Launonen,
- Hanna Laakso,
- Marjo Malinen,
- Einari A. Niskanen,
- Jorma J. Palvimo,
- and Ville Paakinaho
Genome Res. August 2025 35: 1717-1732; Published in Advance June 2, 2025, doi:10.1101/gr.280224.124
...). These data sets suggest a potential direct cross talk between AR and GR that has a different outcome from the GR-driven antiandrogen resistance. To characterize the direct cross talk between AR and GR, we utilized VCaP cells that endogenously express transcriptionally active wild-type AR and GR (Puhr et al...
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Research: Intergenic accumulation of RNA polymerase II maintains the potential for swift transcriptional restart upon release from quiescence
- Manuela Baquero Pérez,
- Gertjan Laenen,
- Isabelle Loïodice,
- Mickaël Garnier,
- Ugo Szachnowski,
- Antonin Morillon,
- Myriam Ruault,
- and Angela Taddei
Genome Res. October 2025 35: 2226-2239; Published in Advance August 12, 2025, doi:10.1101/gr.279874.124
..., and telomere hyperclustering keeps increasing up to 6 days.To test whether hypercluster formation is required for transcriptional shutdown, we examined RNAPII binding in a sir3Δ mutant, defective for hypercluster formation but able to form HD small cells, morphologically similar to the wild type (WT) (Fig. 1C...
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Resource: DEAD box RNA helicases are pervasive protein kinase interactors and activators
- Alexander Hirth,
- Edoardo Fatti,
- Eugen Netz,
- Sergio P. Acebron,
- Dimitris Papageorgiou,
- Andrea Švorinić,
- Cristina-Maria Cruciat,
- Emil Karaulanov,
- Alexandr Gopanenko,
- Tianheng Zhu,
- Irmgard Sinning,
- Jeroen Krijgsveld,
- Oliver Kohlbacher,
- and Christof Niehrs
Genome Res. June 2024 34: 952-966; Published in Advance July 10, 2024, doi:10.1101/gr.278264.123
...export, transcriptional regulation, and maintenance of stability (Jarmoskaite and Russell 2014; Cargill et al. 2021; Bohnsack et al. 2023).One well-characterized RNA helicase is DDX3X, which has a helicase-independent “moonlighting” function during Wnt signaling, in which it acts as a specific activator...
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Research: Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases DDX3X and DDX3Y
- Shruthi Rengarajan,
- Jason Derks,
- Daniel W. Bellott,
- Nikolai Slavov,
- and David C. Page
Genome Res. January 2025 35: 20-30; Published in Advance January 10, 2025, doi:10.1101/gr.279707.124
...observations: In DDX3X-mutant lymphomas in human males, Gong et al. (2021) reported that DDX3Y transcript levels were elevated compared to wild-type lymphocytes (B cells). Gong et al. (2021) speculated that DDX3Y upregulation in these DDX3X-mutant lymphomas reflected an aberrant, oncogenically adaptive gene...
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Research: Epigenetic drift score captures directional methylation variability and links aging to transcriptional, metabolic, and genetic alterations
- Xiu Fan,
- Qili Qian,
- Wenran Li,
- Tianzi Liu,
- Changqing Zeng,
- Peilin Jia,
- Huandong Lin,
- Xin Gao,
- Li Jin,
- Mingfeng Xia,
- Sijia Wang,
- and Fan Liu
Genome Res. October 2025 35: 2173-2188; Published in Advance August 1, 2025, doi:10.1101/gr.280155.124
...,B). Specifically, genes associated with positive drift-CpGs exhibited a tendency towards higher mean expression and discernibly greater expression variability compared to the -wide background, suggesting a relatively more active yet potentially unstable transcriptional state. Conversely, genes adjacent to negative...
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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
...) Quantification of KDM6A protein expression normalized on GAPDH levels in 47,XYY UTY−/− and UTY+/+ iPSCs. Four independent UTY−/− and two UTY+/+ (CTR.) clones (cl.) have been tested. The significance of the comparison between wild-type and knockout samples was calculated using the one-way ANOVA and pairwise...
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Research: Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain
- James L. Shepherdson,
- David M. Granas,
- Jie Li,
- Zara Shariff,
- Stephen P. Plassmeyer,
- Alex S. Holehouse,
- Michael A. White,
- and Barak A. Cohen
Genome Res. October 2024 34: 1540-1552; Published in Advance September 25, 2024, doi:10.1101/gr.279415.124
...chemistry is preserved while local sequence order is altered. Two of the three shuffled variants showed reduced transcriptional activity compared to wild-type CRX, but the third showed the strongest reporter activation of any CRX variant tested (Fig. 5E). From this result, it is clear that the effector...
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Research: Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma
- Winnie S. Liang,
- William Hendricks,
- Jeffrey Kiefer,
- Jessica Schmidt,
- Shobana Sekar,
- John Carpten,
- David W. Craig,
- Jonathan Adkins,
- Lori Cuyugan,
- Zarko Manojlovic,
- Rebecca F. Halperin,
- Adrienne Helland,
- Sara Nasser,
- Christophe Legendre,
- Laurence H. Hurley,
- Karthigayini Sivaprakasam,
- Douglas B. Johnson,
- Holly Crandall,
- Klaus J. Busam,
- Victoria Zismann,
- Valerie Deluca,
- Jeeyun Lee,
- Aleksandar Sekulic,
- Charlotte E. Ariyan,
- Jeffrey Sosman,
- and Jeffrey Trent
Genome Res. April 2017 27: 524-532; doi:10.1101/gr.213348.116
...on average, whereas in tumor cells, 0.2 TERT transcripts can lead to activation, although tumors may express hundreds of TERT transcripts per cell (Yi et al. 2001; Akıncılar et al. 2015). Lastly, our observation that TERT inhibition (in the context of TERT promoter mutation or CNV gain) successfully...

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