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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
...on potentially misleading predictions.Prediction of potential regulatory sitesThis review focuses on gene-specific transcriptional regulation via direct TF binding to regulatory DNA sites. The initial task is thus to locate candidate DNA regions potentially involved in TF binding, and this starts...
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Method: Chromosome engineering to correct a complex rearrangement on Chromosome 8 reveals the effects of 8p syndrome on gene expression and neural differentiation
- Sophia N. Lee,
- Erin C. Banda,
- Lu Qiao,
- Sarah L. Thompson,
- Karan Singh,
- Ryan A. Hagenson,
- Teresa Davoli,
- Stefan F. Pinter,
- and Jason M. Sheltzer
Genome Res. March 2026 36: 547-560; Published in Advance January 12, 2026, doi:10.1101/gr.280425.125
...is not known. To address this question and to further explore the transcriptional consequences of invdupdel(8p), we compared the gene expression profile of the invdupdel(8p) proband, normalized to the revertant, to an iPS cell line with Trisomy 21, normalized to an isogenic diploid clone that arose...
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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
...the inflammatory and immune mechanisms underlying AD progression.Identifying TF–target gene networks involved in AD progressionThe accessibility of chromatin regions to TFs is a major determinant of cellular transcriptional profile (Zhu et al. 2019; Coux et al. 2020; Ren et al. 2021). To identify lineage...
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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
...transcriptional programs. Gene expression is regulated by cis-regulatory elements (CREs) in a spatiotemporal manner through precise gene regulatory networks (Lee and Young 2013; Levine et al. 2014; Long et al. 2016). Understanding these regulatory mechanisms beyond transcription may reveal critical aspects of how...
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Method: Kinetic measurement of gene-specific RNA polymerase II transcription elongation rates
- Haiyue Liu and
- Lea H. Gregersen
Genome Res. November 2025 35: 2550-2562; Published in Advance October 22, 2025, doi:10.1101/gr.280852.125
...point mutations or factor perturbations followed by average RNAPII rate estimation have associated RNAPII speed with functionality, direct measurements of RNAPII transcription elongation rates for individual genes and their correlation with chromatin modifications, RNAPII-associated cofactors, or 3′end...
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Method: Automated chromatin profiling with spa-ChIP-seq uncovers the impacts of condition variations
- Yuwei Cao,
- Lauren Patel,
- Lauren Alcoser,
- Eric Mendenhall,
- Christopher Benner,
- Sven Heinz,
- and Alon Goren
Genome Res. January 2026 36: 129-141; Published in Advance December 12, 2025, doi:10.1101/gr.281320.125
...had highly reproducible SNRs across six of the seven samples, and the variability observed in the remaining sample was within the expected range of experimental variability (Fig. 3A–C). To further assess antibody performance, we profiled signal enrichment around transcription start sites (TSSs...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...magnitude and direction of selective pressure through changes in the extracellular matrix, nutrient availability, immune system cells, cytokines, and T cell regulators (Anari et al. 2018; Mansouri et al. 2022; Nakayama et al. 2022; Otohinoyi et al. 2022).In non-small-cell lung cancer (NSCLC), pronounced...
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Method: k-mer cross-species profiling reveals taxon-specific TE expansions accompanied by KZFP co-option and functional impacts in ruminants
- Pengju Zhao,
- Jiayi He,
- Chen Peng,
- Yuelang Zhang,
- Chong Wang,
- Dongyou Yu,
- Lingzhao Fang,
- and Zhengguang Wang
Genome Res. March 23, 2026 gr.281289.125; Published in Advance March 23, 2026, doi:10.1101/gr.281289.125
...sequences (>100 bp) to ensure k-mer 405 analysis precision. 406 When comparing TE expansion patterns among ruminant species, a major challenge 407 arose: the heterogeneity in TE family expansions across species, combined with sequence 408 variation within TE subfamilies, hindered direct comparative analysis...
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Research: Nanopore direct RNA sequencing reveals METTL2A-mediated m³C sites in poly(A) RNA
- Shuhei Mitsutomi,
- Anzu Sugawara,
- Masahide Seki,
- Yutaka Suzuki,
- Sotaro Miyao,
- Haozhe Du,
- Kenji Takahashi,
- Yusuke Mizukami,
- Kenzui Taniue,
- and Nobuyoshi Akimitsu
Genome Res. November 2025 35: 2406-2417; Published in Advance October 30, 2025, doi:10.1101/gr.280269.124
...sequencing by replacing the standard DNA polymerase with a reverse transcriptase (Vilfan et al. 2013), although this approach has not been widely adopted. Nanopore direct RNA sequencing has made it possible to directly sequence full-length native RNA molecules without reverse transcription and amplification...
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Method: An optimized protocol for quality control of gene therapy vectors using nanopore direct RNA sequencing
- Kathleen Zeglinski,
- Christian Montellese,
- Matthew E. Ritchie,
- Monther Alhamdoosh,
- Cédric Vonarburg,
- Rory Bowden,
- Monika Jordi,
- Quentin Gouil,
- Florian Aeschimann,
- and Arthur Hsu
Genome Res. November 2024 34: 1966-1975; Published in Advance October 28, 2024, doi:10.1101/gr.279405.124
...on which sequencing technology is most effective for quality control (QC) of LVs, and current cDNA sequencing approaches which rely on reverse transcription (RT) of the lentiviral RNA can introduce bias (Schulz et al. 2021).Nanopore direct RNA sequencing is a relatively new technology that enables...

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