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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
..., hinging on the precise binding of transcription factors (TFs) and cofactors to gene regulatory elements such as promoters and enhancers. Although it is relatively routine to profile -wide DNA binding landscapes of proteins, identifying the specific proteins that bind to, and regulate the transcription of...
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Research: Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis
- Olga M. Sigalova,
- Mattia Forneris,
- Frosina Stojanovska,
- Bingqing Zhao,
- Rebecca R. Viales,
- Adam Rabinowitz,
- Fayrouz Hammal,
- Benoît Ballester,
- Judith B. Zaugg,
- and Eileen E.M. Furlong
Genome Res. May 2025 35: 1138-1153; Published in Advance April 15, 2025, doi:10.1101/gr.279652.124
...genetic variation impacts transcription factor (TF) binding remains a major challenge, limiting our ability to model disease-associated variants. Here, we used a highly controlled system of F1 crosses with extensive genetic diversity to profile allele-specific binding of four TFs at several time points...
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Research: Distinct classes of lamina-associated domains are defined by differential patterns of repressive histone methylation
- Caden J. Martin,
- Elizabeth A. Oser,
- Prabakaran Nagarajan,
- Liudmila V. Popova,
- Benjamin D. Sunkel,
- Benjamin Z. Stanton,
- and Mark R. Parthun
Genome Res. September 2025 35: 1959-1974; Published in Advance August 5, 2025, doi:10.1101/gr.280380.124
...actively transcribed genes are found in euchromatin, which is relatively decondensed, enriched in histone acetylation, transcription factor binding, and RNA polymerase II, and largely localizes to the nuclear interior. Heterochromatin is transcriptionally repressive and highly compacted. It comes in two...
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Method: Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data
- Kaixuan Luo,
- Jianling Zhong,
- Alexias Safi,
- Linda K. Hong,
- Alok K. Tewari,
- Lingyun Song,
- Timothy E. Reddy,
- Li Ma,
- Gregory E. Crawford,
- and Alexander J. Hartemink
Genome Res. June 2022 32: 1183-1198; Published in Advance May 24, 2022, doi:10.1101/gr.272203.120
...in different types of cells and under different conditions. This response of a cell's gene expression to its internal and external context is enacted in large part through the tuned occupancy of transcription factors (TFs) across the . To understand how TFs regulate gene expression, it is critical to determine...
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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
....To further analyze the data, we performed Gene Ontology (GO) enrichment analysis on differentially expressed genes and transcription factor (TF) binding site motif analysis on differential ATAC-seq peaks (Bailey et al. 2015; Kolberg et al. 2023). GO terms associated with increased gene expression...
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Research: Xist upstream deletion leads to dysregulation of Xist and autosomal gene expression
- Sudeshna Majumdar,
- Lakshmi Sowjanya Bammidi,
- Hemant C. Naik,
- Avinchal Manhas,
- Runumi Baro,
- Akash Kalita,
- Amlan Jyoti Naskar,
- Sundarraj Nidharshan,
- Girija S. Bariha,
- Dimple Notani,
- and Srimonta Gayen
Genome Res. September 2025 35: 1992-2010; Published in Advance August 6, 2025, doi:10.1101/gr.279822.124
...Xist nuclei, it intrigued us to explore the status of X-linked gene silencing on the inactive X. For this, we performed allele-specific RNA-seq analysis for the WT clones, WT EV clones, D1 ΔXp, and D3 ΔXpΔXm XEN cells. As expected, both in WT clones and WT EV clones, X-linked genes showed exclusive...
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Research: Differences in activity and stability drive transposable element variation in tropical and temperate maize
- Shujun Ou,
- Armin Scheben,
- Tyler Collins,
- Yinjie Qiu,
- Arun S. Seetharam,
- Claire C. Menard,
- Nancy Manchanda,
- Jonathan I. Gent,
- Michael C. Schatz,
- Sarah N. Anderson,
- Matthew B. Hufford,
- and Candice N. Hirsch
Genome Res. August 2024 34: 1140-1153; Published in Advance September 9, 2024, doi:10.1101/gr.278131.123
...of transcript abundance challenging on a per-element basis. We therefore evaluated transcript abundance on a per-family basis within each , as previously described (Anderson et al. 2019), and conducted differential expression analysis between tropical and temperate s (Supplemental Fig. S12A,B). The total...
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Research: Copy number variation alters local and global mutational tolerance
- Grace Avecilla,
- Pieter Spealman,
- Julia Matthews,
- Elodie Caudal,
- Joseph Schacherer,
- and David Gresham
Genome Res. August 2023 33: 1340-1353; Published in Advance August 31, 2023, doi:10.1101/gr.277625.122
...) (Supplemental Table S8). As our sequencing and analysis pipeline cannot differentiate between recurrent insertion events and PCR duplicates, we quantified the number of unique insertion sites per gene, unless otherwise noted (Supplemental Tables S9, S10). The nine libraries showed variation in the number...
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Method: Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets
- Alexander Morin,
- Eric Ching-Pan Chu,
- Aman Sharma,
- Alex Adrian-Hamazaki,
- and Paul Pavlidis
Genome Res. May 2023 33: 763-778; Published in Advance June 12, 2023, doi:10.1101/gr.277273.122
...IP-seq of TRs and experiments that perturb a TR and measure the differential abundance of gene transcripts are a primary means by which direct relationships are tested on a genomic scale. It has been reported that there is a poor overlap in the evidence across gene regulation strategies, emphasizing the need...
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Research: AP-1 subunits converge promiscuously at enhancers to potentiate transcription
- Jungkyun Seo,
- D. Dewran Koçak,
- Luke C. Bartelt,
- Courtney A. Williams,
- Alejandro Barrera,
- Charles A. Gersbach,
- and Timothy E. Reddy
Genome Res. April 2021 31: 538-550; Published in Advance March 5, 2021, doi:10.1101/gr.267898.120
...were able to determine the genomic binding of each subunit at its native expression level in a way that controls for variation in antibody affinity and specificity. Further, to relate changes in AP-1 subunit occupancy to changes in gene regulation, we focused on the genomic response to glucocorticoids...
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