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Method: High-resolution spatial transcriptomics in fixed tissue using a cost-effective PCL-seq workflow
- Xue Dong,
- Mengzhu Hu,
- Xiaonan Cui,
- Wenjian Zhou,
- Jingtao Cai,
- Guangyao Mao,
- and Weiyang Shi
Genome Res. September 2025 35: 2052-2063; Published in Advance August 5, 2025, doi:10.1101/gr.279906.124
...photocleavable oligonucleotides and ligation adapters to construct transcriptional profiles of specific regions of interest (ROIs) designated via microscopically controlled photo-illumination. In frozen mouse embryos, PCL-seq generates spatially aligned gene expression matrices and produces high-quality data...
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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: Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions
- Yuning Zhang,
- Tiffany D. Ho,
- Nicolas E. Buchler,
- and Raluca Gordân
Genome Res. July 2021 31: 1216-1229; Published in Advance May 11, 2021, doi:10.1101/gr.275145.120
...) and Microphthalmia-associated transcription factor (MITF) subfamilies in animals as the likely descendants of these Pho4-like and Cbf1-like progenitors, respectively. The conservation of specific amino acids in each subfamily DNA-binding domain (Supplemental Fig. S1A) suggests that binding preferences of these TFs...
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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
...-based transcriptional regulatory networks. Overall, these results illustrate the power of an approach combining genetic perturbation with high-resolution epigenomic profiling; the latter enables a close examination of the interplay between TFs and nucleosomes -wide, providing a deeper, more mechanistic understanding...
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Method: Genome-wide maps of CPD deamination in yeast reveal the impact of DNA sequence context and nucleosome architecture on cytosine deamination rates
- Marian F. Laughery,
- Bastian Stark,
- Benjamin Morledge-Hampton,
- Steven A. Roberts,
- and John J. Wyrick
Genome Res. January 2026 36: 183-196; Published in Advance December 9, 2025, doi:10.1101/gr.280384.124
...observed significantly higher SASAC4 (for hydroxide) at minor-in positions relative to minor-out in the yeast nucleosome structure and other high-resolution nucleosome structures (Fig. 6C; Supplemental Fig. S10E,F). At minor-in rotational settings, the minor groove of the DNA faces toward the histone...
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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
...al. 2005; Potthoff and Olson 2007; Zdobnov et al. 2020), with highly conserved DNA-binding domains (Carlsson and Mahlapuu 2002; Chang et al. 2015).View larger version: In this window In a new window Figure 1. Profiling transcription factor (TF) binding in F1 embryos of Drosophila melanogaster. (A...
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Resource: Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships
- Michelle Kudron,
- Louis Gevirtzman,
- Alec Victorsen,
- Bridget C. Lear,
- Jiahao Gao,
- Jinrui Xu,
- Swapna Samanta,
- Emily Frink,
- Adri Tran-Pearson,
- Chau Huynh,
- Dionne Vafeados,
- Ann Hammonds,
- William Fisher,
- Martha Wall,
- Greg Wesseling,
- Vanessa Hernandez,
- Zhichun Lin,
- Mary Kasparian,
- Kevin White,
- Ravi Allada,
- Mark Gerstein,
- LaDeana Hillier,
- Susan E. Celniker,
- Valerie Reinke,
- and Robert H. Waterston
Genome Res. December 2024 34: 2319-2334; Published in Advance October 22, 2024, doi:10.1101/gr.279037.124
.... Critically, they also permit the mapping of TF binding in the living organism, which is not straightforward for human TFs. Many TFs in these two species are orthologous to human TFs. To a significant extent, they encompass the same broad classes of DNA-binding domains, exhibit similar functions, respond...
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Research: Genome-wide determinants of sequence-specific DNA binding of general regulatory factors
- Matthew J. Rossi,
- William K.M. Lai,
- and B. Franklin Pugh
Genome Res. April 2018 28: 497-508; Published in Advance March 21, 2018, doi:10.1101/gr.229518.117
...binding sites (Gordan et al. 2013). The same motif is bound by the transcription factor Pho4, yet the two possess distinct specificities despite having the same class of basic helix-loop-helix DNA binding domain and core recognition sequence (Zhou and O'Shea 2011). We therefore compared the DNA sequence...
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Research: Spatiotemporal kinetics of CAF-1-dependent chromatin maturation ensures transcription fidelity during S-phase
- Boning Chen,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. December 2023 33: 2108-2118; Published in Advance December 11, 2023, doi:10.1101/gr.278273.123
...U-labeled DNA fragments were biotinylated with click chemistry and enriched using streptavidin–biotin isolation before being subjected to paired-end sequencing. DNA fragments protected by the histone octamer should be ∼150 bp in length, whereas small DNA binding factors such as transcription factors...
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Method: Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions
- Alicia N. Schep,
- Jason D. Buenrostro,
- Sarah K. Denny,
- Katja Schwartz,
- Gavin Sherlock,
- and William J. Greenleaf
Genome Res. November 2015 25: 1757-1770; Published in Advance August 27, 2015, doi:10.1101/gr.192294.115
...Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions Alicia N. Schep 1 , Jason D. Buenrostro 1 , Sarah K. Denny 2 , Katja Schwartz 1 , Gavin Sherlock 1 and William J...
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