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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...: In this window In a new window Figure 5. R3 activity alters chromatin looping surrounding MYH6 and MYH7. (A,B) Contact frequency between the MYH6 TSS and R3 (A) or C3 (B), normalized to total contacts in the region, as represented in panels C–H. (C–H) Differential contact maps showing the impact of R3 activity...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...disease susceptibility. This approach goes beyond characterizing gene regulatory variation in static, postmortem tissue and opens new avenues for studying GxE interactions in a controlled, in vitro setting.ResultsWe differentiated brain organoids from the induced pluripotent stem cells (iPSCs) of 21...
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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
...populations in ALS mice and wild-type littermates and confirmed differential gene expression (DEG) using RNAscope. We also conducted machine learning, using the random forest classifier and Lasso regression, to identify strong disease predictors across the SOD1 mutations and species, as well as a meta...
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Method: Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity
- Mayank Murali,
- Jamie Saquing,
- Senbao Lu,
- Ziyang Gao,
- Emily F. Watts,
- Ben Jordan,
- Zachary Peters Wakefield,
- Ana Fiszbein,
- David R. Cooper,
- Peter J. Castaldi,
- Dmitry Korkin,
- and Gloria M. Sheynkman
Genome Res. April 2025 35: 1012-1024; Published in Advance March 14, 2025, doi:10.1101/gr.279317.124
...the protein-level impact of variations not commonly described: codons that span junctions and unusual reading frame shifts.To characterize differentially split codons, we examined all paired codons (see c-block section in Methods) that are split across junctions and determined the identity of the associated...
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Research: Evidence for compensatory evolution within pleiotropic regulatory elements
- Zane Kliesmete,
- Peter Orchard,
- Victor Yan Kin Lee,
- Johanna Geuder,
- Simon M. Krauß,
- Mari Ohnuki,
- Jessica Jocher,
- Beate Vieth,
- Wolfgang Enard,
- and Ines Hellmann
Genome Res. October 2024 34: 1528-1539; Published in Advance September 10, 2024, doi:10.1101/gr.279001.124
...family members.The impact of pleiotropy on the evolutionary conservation of regulatory activityTo investigate the relationship between CRE PD and their evolutionary conservation, we generated RNA-seq and ATAC-seq data from iPSC-derived NPCs from humans and cynomolgus macaques (Supplemental Fig. S3A...
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Resource: Genome-wide identification of tandem repeats associated with splicing variation across 49 tissues in humans
- Kohei Hamanaka,
- Daisuke Yamauchi,
- Eriko Koshimizu,
- Kei Watase,
- Kaoru Mogushi,
- Kinya Ishikawa,
- Hidehiro Mizusawa,
- Naomi Tsuchida,
- Yuri Uchiyama,
- Atsushi Fujita,
- Kazuharu Misawa,
- Takeshi Mizuguchi,
- Satoko Miyatake,
- and Naomichi Matsumoto
Genome Res. March 2023 33: 435-447; Published in Advance March 27, 2023, doi:10.1101/gr.277335.122
...associations (P-value threshold: CACNA1A, 5 × 10−6; PPP2R2B, 4 × 10−6; see Methods subsection “Identification of all significant TR–splicing pairs in each gene”). (Second panel from the top) iPSC-derived neurons of an SCA12 patient with 14/60 CAG repeats and a healthy individual with 9/16 units are shown (C...
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Method: Predicting genotype-specific gene regulatory networks
- Deborah Weighill,
- Marouen Ben Guebila,
- Kimberly Glass,
- John Quackenbush,
- and John Platig
Genome Res. March 2022 32: 524-533; Published in Advance February 22, 2022, doi:10.1101/gr.275107.120
.... There is, however, recent evidence that disease-associated genetic variants impact gene regulation, and thus expression, by disrupting transcription factor (TF) binding (Kalita et al. 2018; Vierstra et al. 2020). In addition, work by van de Geijn and colleagues has shown that genetic variation...
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Resource: Comparing genomic and epigenomic features across species using the WashU Comparative Epigenome Browser
- Xiaoyu Zhuo,
- Silas Hsu,
- Deepak Purushotham,
- Prashant Kumar Kuntala,
- Jessica K. Harrison,
- Alan Y. Du,
- Samuel Chen,
- Daofeng Li,
- and Ting Wang
Genome Res. May 2023 33: 824-835; Published in Advance May 8, 2023, doi:10.1101/gr.277550.122
...using the browser to display the association between epigenomic changes with a SNP (Fig. 4A). Recently, we characterized SVs between human and chimpanzee and their impact on the epi (Zhuo et al. 2020). Figure 5A illustrates an interesting case of human-specific TE-derived putative enhancer we identified...
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Resource: Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish
- Hyung Joo Lee,
- Yiran Hou,
- Ju Heon Maeng,
- Nakul M. Shah,
- Yujie Chen,
- Heather A. Lawson,
- Hongbo Yang,
- Feng Yue,
- and Ting Wang
Genome Res. July 2022 32: 1424-1436; Published in Advance June 1, 2022, doi:10.1101/gr.276052.121
..., Institute of Reproduction and Development, Fudan University, Shanghai 200437, China Corresponding authors: twang@wustl.edu, yue@northwestern.edu, hongboyang@fudan.edu.cnAbstractTransposable elements (TEs) encode regulatory elements that impact gene expression in multiple species, yet a comprehensive...
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Method: Epigenomic differences in the human and chimpanzee genomes are associated with structural variation
- Xiaoyu Zhuo,
- Alan Y. Du,
- Erica C. Pehrsson,
- Daofeng Li,
- and Ting Wang
Genome Res. February 2021 31: 279-290; Published in Advance December 10, 2020, doi:10.1101/gr.263491.120
...of regulatory elements during evolution (Xiao et al. 2012; Lowdon et al. 2016). Although studies have investigated enhancer evolution between human and chimpanzee (Gallego Romero et al. 2015; Prescott et al. 2015; Trizzino et al. 2017; Ward et al. 2018), the impact of SV on these elements has not been studied...

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