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Resource: Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease
- Yunxiao Ren,
- Ming Hu,
- Yang E. Li,
- Andrew A. Pieper,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. March 2026 36: 645-659; Published in Advance January 21, 2026, doi:10.1101/gr.280436.125
...–specific TFs in regulating key genes associated with AD progression, linking transcriptional changes to genetic risk loci and highlighting potential mechanisms underlying disease pathology.View larger version: In this window In a new window Figure 5. Cell type–specific TF regulatory network. (A) TF regulatory...
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Method: Iterative improvement of deep learning models using synthetic regulatory genomics
- André M. Ribeiro-dos-Santos and
- Matthew T. Maurano
Genome Res. November 2025 35: 2539-2549; Published in Advance October 22, 2025, doi:10.1101/gr.280540.125
...the reference, such as disease- and trait-associated variants or engineered sequences. Recent work has applied synthetic regulatory genomics to characterized dozens of deletions, inversions, and rearrangements of DNase I hypersensitive sites (DHSs). Here, we use the state-of-the-art model Enformer to predict...
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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M Riley,
- Randa Elsayed,
- Mark D Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C Nelson
Genome Res. March 4, 2026 gr.280838.125; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...consistent developmental outcomes 26 between species, similar gene regulatory programmes and gene expression patterns must 27 also be maintained. The endoderm germ layer makes major contributions to the respiratory 28 and gastrointestinal tracts, and associated organs including liver and pancreas. We used 29...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...is crucial for distinguishing regulatory mechanisms at a GOI that are differentially regulated in different cell types in a complex tissue. A key highlight of FISH is that it provides spatial resolution and the ability to focus on specific transcripts, dissecting transcriptional regulation from potential...
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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
...-characterized pathways. As mentioned in the previous subsection, the deletion of GAL80 (gal80Δ) caused significant changes to the chromatin structure of the GAL loci, and we now found it was also associated with transcriptional changes, particularly at GAL1, GAL10, and GAL2 (Figs. 2C,D, 3C; Supplemental Figs. S6, S8...
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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
...of this regulatory element on cell function and the cellular stress response. Lastly, we identify genetic variants within this enhancer that are associated with cardiac disease. These findings support a novel mechanism of myosin gene regulation and implicate myosin expression in regulating the CM response to stress...
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Research: Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance
- Yang Xi,
- Jingjing Qi,
- Zhao Yang,
- Yutian Zeng,
- Huicong Zhang,
- Qiuyu Tao,
- Mengru Xu,
- Anqi Huang,
- Shenqiang Hu,
- Chunchun Han,
- Lili Bai,
- Jiwei Hu,
- Jiwen Wang,
- Liang Li,
- Lingzhao Fang,
- and Hehe Liu
Genome Res. October 2025 35: 2211-2225; Published in Advance September 10, 2025, doi:10.1101/gr.280345.124
...are known to play important roles in eggshell formation in poultry (Liu et al. 2013; Marie et al. 2015). These findings suggest that variations in egg production in the current population are closely associated with transcriptional regulatory changes in multiple tissues, especially in the shell gland...
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Method: Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes
- Rachel M. Petersen,
- Christopher M. Vockley,
- and Amanda J. Lea
Genome Res. August 2025 35: 1781-1793; Published in Advance July 14, 2025, doi:10.1101/gr.279957.124
...elements is modulated by methylation, which is generally associated with decreased transcription. Within our set of regulatory elements, we use allele-specific expression analyses to identify 8020 sites with genetic effects on gene regulation; further, we find that 42.3% of these genetic effects vary...
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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
...brain organoids to hypoxic and hyperoxic conditions, we identify hundreds of gene regulatory changes that are undetectable under baseline conditions, with 148 trait-associated genes showing regulatory effects only in response to oxygen stress. To capture more nuanced transcriptional patterns, we employ...
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Resource: Charting the regulatory landscape of TP53 on transposable elements in cancer
- Xuan Qu,
- Yonghao Liang,
- Colin McCornack,
- Xiaoyun Xing,
- Heather Schmidt,
- Chad Tomlinson,
- Catrina Fronick,
- Edward A. Belter, Jr.,
- Juan F. Macias-Velasco,
- and Ting Wang
Genome Res. June 2025 35: 1456-1471; Published in Advance May 13, 2025, doi:10.1101/gr.279398.124
...Fig. S3I).In summary, TP53 induces a specific TE-derived transcriptional profile, with active transcription-initiating TE loci mainly residing in LINE and LTR elements. Upon doxorubicin-induced TP53 activation, we observed a more transcriptionally active landscape, with a higher number of DETs between...
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