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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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Method: Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation
- Richa Rashmi,
- Abhinaya Muruganandham,
- Pranita Borkar,
- Sumana Mallick,
- Taylor Hubbs,
- Ari Aviles,
- Daniel Chung,
- and Irtisha Singh
Genome Res. April 13, 2026 gr.281044.125; Published in Advance April 13, 2026, doi:10.1101/gr.281044.125
...a regulatory axis connecting epigenetic 23 state and IPA. This finding aligns with emerging evidence that DNA methylation modulates 24 2 alternative polyadenylation via CTCF-mediated chromatin looping. Thus, IPAseek provides a 25 platform to characterize IPA across physiological systems and disease contexts...
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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
...-induced DNA damage (Andrade-Lima et al. 2015; Williamson et al. 2017; Cugusi et al. 2022). In addition, dysregulated transcriptional elongation has been implicated in developmental defects as well as disease and aging (Aoi and Shilatifard 2023; Debès et al. 2023).RNAPII elongation rates not only reflect...
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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
...by 30%–50%. This fine-grained “mutagenesis” can reconstruct functionalized binding motifs for all factors. To prioritize causal variants, we trained a convolutional neural network (Basenji) to accurately predict binding from DNA sequence. The model can also predict measured allelic imbalance for strong...
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Method: TFcomb identifies transcription factor combinations for cellular reprogramming based on single-cell multiomics data
- Chen Li,
- Sijie Chen,
- Yixin Chen,
- Haiyang Bian,
- Minsheng Hao,
- Lei Wei,
- and Xuegong Zhang
Genome Res. June 2025 35: 1429-1439; Published in Advance April 10, 2025, doi:10.1101/gr.279955.124
...for each gene. Then the DNA sequence of each correlated peak is used to scan TFs with the gimmemotifs v.5 vertebrate motif data set (https://gimmemotifs.readthedocs.io/en/master/). For the TFs that are not included in the gimmemotifs database, we searched the corresponding motifs in JASPAR database...
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Method: Unraveling the palindromic and nonpalindromic motifs of retroviral integration site sequences by statistical mixture models
- Dalibor Miklík,
- Jiří Grim,
- Daniel Elleder,
- and Jiří Hejnar
Genome Res. August 2023 33: 1395-1408; Published in Advance July 18, 2023, doi:10.1101/gr.277694.123
...of the transcription factor to the other half-site of the motif (Datta and Rister 2022). Unlike the motifs of transcription factors, retroviral IS motifs are limited to a few positions and are probably not the consequence of the sequence-specific IN–tDNA interactions. However, we showed that the presence...
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Method: A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma
- Jan Müller,
- Christina Hartwig,
- Mirko Sonntag,
- Lisa Bitzer,
- Christopher Adelmann,
- Yevhen Vainshtein,
- Karolina Glanz,
- Sebastian O. Decker,
- Thorsten Brenner,
- Georg F. Weber,
- Arndt von Haeseler,
- and Kai Sohn
Genome Res. August 2024 34: 1185-1195; Published in Advance September 13, 2024, doi:10.1101/gr.279326.124
...is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we find significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA methylation, positively with H3K4me...
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Research: Assessing DNA methylation detection for primary human tissue using Nanopore sequencing
- Rylee Genner,
- Stuart Akeson,
- Melissa Meredith,
- Pilar Alvarez Jerez,
- Laksh Malik,
- Breeana Baker,
- Abigail Miano-Burkhardt,
- CARD-long-read Team,
- Benedict Paten,
- Kimberley J. Billingsley,
- Cornelis Blauwendraat,
- and Miten Jain
Genome Res. April 2025 35: 632-643; Published in Advance March 7, 2025, doi:10.1101/gr.279159.124
...the addition of a methyl group to the fifth carbon of a cytosine residue to form a 5mC (5-methylcytosine) complex. This reversible reaction is catalyzed by DNA methyltransferases (DNMTs) and is positively correlated with the recruitment of histone proteins that compact the DNA structure, making it inaccessible...
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Research: Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription
- Christine R. Keenan,
- Hannah D. Coughlan,
- Nadia Iannarella,
- Andres Tapia del Fierro,
- Andrew Keniry,
- Timothy M. Johanson,
- Wing Fuk Chan,
- Alexandra L. Garnham,
- Lachlan W. Whitehead,
- Marnie E. Blewitt,
- Gordon K. Smyth,
- and Rhys S. Allan
Genome Res. April 2024 34: 556-571; Published in Advance May 6, 2024, doi:10.1101/gr.279119.124
...). Given the binary nature of the EDD analysis in calling LADs, we also identified LADs using circular binary segmentation (CBS) to segment DNA with the DNAcopy package (Seshan and Olshen 2023) and the methods in LADetector (Harr et al. 2015; Luperchio et al. 2017). We used this method to assign...
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Research: Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells
- Belle A. Moyers,
- E. Christopher Partridge,
- Mark Mackiewicz,
- Michael J. Betti,
- Roshan Darji,
- Sarah K. Meadows,
- Kimberly M. Newberry,
- Laurel A. Brandsmeier,
- Barbara J. Wold,
- Eric M. Mendenhall,
- and Richard M. Myers
Genome Res. November 2023 33: 1879-1892; Published in Advance October 18, 2023, doi:10.1101/gr.278205.123
...of the human cell line HepG2 and show the usefulness of large genomic analyses for elucidation of individual TF functions.Gene expression is regulated and modulated by the association, either direct or indirect, of various classes of proteins to DNA, including RNA polymerase and transcription...
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