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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
...regulation. By critically examining both established tools and emerging techniques such as editing, synthetic chromosomes, and high-resolution imaging, we provide a practical framework for investigators seeking to uncover direct regulators of specific genes. Our goal is to guide the design of experiments...
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Method: High-fidelity bidirectional translation between single-cell transcriptomes and DNA methylomes with scBOND
- Kehan Lang,
- Chenyang Jia,
- Siyu Li,
- Yi Guo,
- Dingjun Hu,
- and Shengquan Chen
Genome Res. April 2026 36: 769-784; Published in Advance March 26, 2026, doi:10.1101/gr.281350.125
...their applicability in scenarios that require reverse cross-modality translation; (2) existing methods fall short in modeling the intricate and highly cell-type-specific associations between DNA methylation and gene expression, which exhibit substantial variability across diverse genomic contexts; (3) most existing...
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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. April 2026 36: 695-712; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...and to associated organs including the liver and pancreas. We used functional genomic approaches to identify highly conserved endodermal cis-regulatory modules (CRMs) functioning across the 400 million years of evolution separating zebrafish and humans. Our analyses suggest that there are few endoderm-specific CRMs...
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Research: ACTB methylation regulates SMARCA4 genomic occupancy to promote translation and reduce adhesion in colorectal cancer cells
- Elina Abaev-Schneiderman,
- Linh Nguyen,
- Raz Shalev,
- Tzofit Elbaz Biton,
- Anand Chopra,
- Giritharan Jagadeesan,
- Daniel Sevilla-Sanchez,
- Nili Tickotsky Moskovitz,
- Liron Levin,
- Michal Feldman,
- Capucine Van Rechem,
- and Dan Levy
Genome Res. April 2026 36: 684-694; Published in Advance March 25, 2026, doi:10.1101/gr.280534.125
...polymerization and smooth muscle contraction. Here, we show that the genomic distribution of ACTB is SETD3-dependent and that this regulation modulates the transcription of genes involved in cell adhesion and mRNA translation in colorectal cancer cells. Proteomic analyses reveal that ACTB and SETD3 interact...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. April 2026 36: 849-864; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...as previously described (Zemke et al. 2023). For each sample, approximately 18,000 nuclei were loaded onto a 10x Chromium Controller following the Chromium Next GEM Single Cell Multiome ATAC + Gene Expression User Guide (CG000338, 10x Genomics). Libraries underwent shallow sequencing (∼1–5 million reads per...
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Method: Mapping and quantifying nascent transcript start sites using TT-TSS-seq
- Eleanor Elgood Hunt,
- Claudia Vivori,
- Richard Mitter,
- Vedis Agnadottir,
- and Folkert J. van Werven
Genome Res. March 2026 36: 600-610; Published in Advance February 17, 2026, doi:10.1101/gr.280726.125
....ymeth.2019.10.003 ↵Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CAM, Taylor MS, Engström PG, Frith MC, et al. 2006. Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38: 626–635. doi:10.1038/ng1789 ↵Chia M, Li C, Marques S, Pelechano V...
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Method: EnDeep4mC predicts DNA N⁴-methylcytosine sites using a dual-adaptive feature encoding framework in deep ensembles
- Shuyu Zhang,
- Quan Zou,
- Mengting Niu,
- Zhibin Lv,
- Antony Stalin,
- and Ximei Luo
Genome Res. March 2026 36: 589-599; Published in Advance February 17, 2026, doi:10.1101/gr.280977.125
...) it systematically elucidates species-feature associations and reveals 4mC sequence functional differentiation in biological evolution from a eukaryote/prokaryote perspective, offering potential biological insights that could guide future adaptive encoding strategies.The following sections first detail the Methods...
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Method: Early feature extraction drives model performance in high-resolution chromatin accessibility prediction
- Aayush Grover,
- Till Muser,
- Liine Kasak,
- Lin Zhang,
- Ekaterina Krymova,
- and Valentina Boeva
Genome Res. March 2026 36: 619-629; Published in Advance January 12, 2026, doi:10.1101/gr.281042.125
...for genomic data. Integrated into diverse architectures such as convoluted neural networks (CNNs), long short-term memory (LSTM), dilated CNNs, and transformers, ConvNeXt V2 blocks consistently improve performance, leading to similar prediction accuracy across these different model types. This reveals...
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Research: Transposable elements contribute to the evolution of host shift–related genes in cactophilic Drosophila species
- Daniel Siqueira de Oliveira,
- Anaïs Larue,
- William Vilas Boas Nunes,
- Francois Sabot,
- Alejandra Bodelón,
- María Pilar García Guerreiro,
- Cristina Vieira,
- and Claudia Marcia Aparecida Carareto
Genome Res. March 2026 36: 487-505; Published in Advance February 10, 2026, doi:10.1101/gr.280463.125
...Barcelona, Spain Corresponding authors: claudia.carareto@unesp.br, cristina.vieira@univ.lyon1.frAbstractHost shifts in insects are considered a key process with the potential to contribute to reproductive isolation and speciation. Both genomic and transcriptomic variation are attributed to such a process...
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Research: Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
- Marcel Tarbier,
- Sebastian D. Mackowiak,
- Vaishnovi Sekar,
- Franziska Bonath,
- Etka Yapar,
- Bastian Fromm,
- Omid R. Faridani,
- Inna Biryukova,
- and Marc R. Friedländer
Genome Res. February 2026 36: 291-302; Published in Advance January 12, 2026, doi:10.1101/gr.279914.124
...of microRNA dynamics at the single-cell level.microRNAs (miRNAs) are ∼22 nucleotide (nt) small noncoding RNAs that guide Argonaute effector proteins to target mRNAs in a sequence-specific manner, leading to their translational inhibition and increased degradation through deadenylation and decapping (Bartel...
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