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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
...approaches preceding the availability of structural data. PWM-based predictions depend on databases like TRANSFAC (Matys et al. 2006) and JASPAR (Khan et al. 2018). Modern high-throughput techniques that experimentally identify protein–DNA binding, such as ChIP-seq, SELEX, and protein-binding microarrays...
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RECOMB 2022 Special/Methods: Learning probabilistic protein–DNA recognition codes from DNA-binding specificities using structural mappings
- Joshua L. Wetzel,
- Kaiqian Zhang,
- and Mona Singh
Genome Res. September 2022 32: 1776-1786; Published in Advance September 19, 2022, doi:10.1101/gr.276606.122
...for understanding gene regulation. Although DNA-binding specificities for thousands of transcription factors (TFs) have been determined, the specific amino acid–base interactions comprising their structural interfaces are largely unknown. This lack of resolution hampers attempts to leverage these data in order...
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Resource: A ChIP-exo screen of 887 Protein Capture Reagents Program transcription factor antibodies in human cells
- William K.M. Lai,
- Luca Mariani,
- Gerson Rothschild,
- Edwin R. Smith,
- Bryan J. Venters,
- Thomas R. Blanda,
- Prashant K. Kuntala,
- Kylie Bocklund,
- Joshua Mairose,
- Sarah N. Dweikat,
- Katelyn Mistretta,
- Matthew J. Rossi,
- Daniela James,
- James T. Anderson,
- Sabrina K. Phanor,
- Wanwei Zhang,
- Zibo Zhao,
- Avani P. Shah,
- Katherine Novitzky,
- Eileen McAnarney,
- Michael-C. Keogh,
- Ali Shilatifard,
- Uttiya Basu,
- Martha L. Bulyk,
- and B. Franklin Pugh
Genome Res. September 2021 31: 1663-1679; Published in Advance August 23, 2021, doi:10.1101/gr.275472.121
..., and specificity for cell types and states.ResultsScreening PCRP mAbs by ChIP-exoWe used the massively parallel ChIP-exo version of ChIP-seq to screen PCRP Abs in a 96-well plate format (48 at a time) for their ability to recognize their putative protein targets in a chromatinized, cellular context (Rhee and Pugh...
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Method: Mapping functional transcription factor networks from gene expression data
- Brian C. Haynes,
- Ezekiel J. Maier,
- Michael H. Kramer,
- Patricia I. Wang,
- Holly Brown,
- and Michael R. Brent
Genome Res. August 2013 23: 1319-1328; Published in Advance May 1, 2013, doi:10.1101/gr.150904.112
...binding data from ChIP, evolutionary conservation, and PWM models of binding specificity. The latter can be derived by several experimental methods, including protein binding arrays (Zhu et al. 2009), Selex ( Jolma et al. 2010), and yeast one-hybrid assays (Reece-Hoyes et al. 2011). Interestingly...
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Method: Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes
- Rachel M. Petersen,
- Christopher M. Vockley,
- and Amanda J. Lea
Genome Res. August 2025 35: 1781-1793; Published in Advance July 14, 2025, doi:10.1101/gr.279957.124
...bind to methylated sequences (Hu et al. 2013). Just above our significance threshold, both NRF1 and ZFP809 (FDR adjusted P-values = 0.18) were also enriched near sites with greater ASE in methylated condition. NRF1 is part of the bZIP TF family, which has been demonstrated via SELEX binding assays...
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Resource: PRISM offers a comprehensive genomic approach to transcription factor function prediction
- Aaron M. Wenger,
- Shoa L. Clarke,
- Harendra Guturu,
- Jenny Chen,
- Bruce T. Schaar,
- Cory Y. McLean,
- and Gill Bejerano
Genome Res. May 2013 23: 889-904; Published in Advance February 4, 2013, doi:10.1101/gr.139071.112
...for further experimental exploration. Recent technologies including protein binding microarrays (Berger et al. 2008), highthroughput SELEX ( Jolma et al. 2010), and ChIP-seq itself have facilitated the quantification of the binding preferences of hundreds of different TFs.Meanwhile, decades of protein...
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Method: SelexGLM differentiates androgen and glucocorticoid receptor DNA-binding preference over an extended binding site
- Liyang Zhang,
- Gabriella D. Martini,
- H. Tomas Rube,
- Judith F. Kribelbauer,
- Chaitanya Rastogi,
- Vincent D. FitzPatrick,
- Jon C. Houtman,
- Harmen J. Bussemaker,
- and Miles A. Pufall
Genome Res. January 2018 28: 111-121; Published in Advance December 1, 2017, doi:10.1101/gr.222844.117
...sites and regulate similarly distinct sets of target genes. To address this paradox, we determined the intrinsic specificities of the AR and GR DNA-binding domains using a refined version of SELEX-seq. We developed an algorithm, SelexGLM, that quantifies binding specificity over a large (31-bp) binding...
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Research: Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
- Charles E. Vejnar,
- Mario Abdel Messih,
- Carter M. Takacs,
- Valeria Yartseva,
- Panos Oikonomou,
- Romain Christiano,
- Marlon Stoeckius,
- Stephanie Lau,
- Miler T. Lee,
- Jean-Denis Beaudoin,
- Damir Musaev,
- Hiba Darwich-Codore,
- Tobias C. Walther,
- Saeed Tavazoie,
- Daniel Cifuentes,
- and Antonio J. Giraldez
Genome Res. July 2019 29: 1100-1114; Published in Advance June 21, 2019, doi:10.1101/gr.245159.118
...capture has revealed a set of proteins in intimate contact with mRNAs across different eukaryotic systems (Baltz et al. 2012; Castello et al. 2012; Kwon et al. 2013; Sysoev et al. 2016; Wessels et al. 2016; Despic et al. 2017). In vitro affinity selection methods, such as SELEX (Blackwell and Weintraub...
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Method: A novel k-mer set memory (KSM) motif representation improves regulatory variant prediction
- Yuchun Guo,
- Kevin Tian,
- Haoyang Zeng,
- Xiaoyun Guo,
- and David Kenneth Gifford
Genome Res. June 2018 28: 891-900; Published in Advance April 13, 2018, doi:10.1101/gr.226852.117
...and Stormo 2014), Slim (Keilwagen and Grau 2015), and TFFM (Mathelier and Wasserman 2013) motif models in predicting in vitro TF binding sites using HTSELEX data (Jolma et al. 2013). The various motif models were trained using ChIP-seq binding data as above. For the TFs that were profiled in both HT-SELEX...
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Research: Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants
- Metewo Selase Enuameh,
- Yuna Asriyan,
- Adam Richards,
- Ryan G. Christensen,
- Victoria L. Hall,
- Majid Kazemian,
- Cong Zhu,
- Hannah Pham,
- Qiong Cheng,
- Charles Blatti,
- Jessie A. Brasefield,
- Matthew D. Basciotta,
- Jianhong Ou,
- Joseph C. McNulty,
- Lihua J. Zhu,
- Susan E. Celniker,
- Saurabh Sinha,
- Gary D. Stormo,
- Michael H. Brodsky,
- and Scot A. Wolfe
Genome Res. June 2013 23: 928-940; Published in Advance March 7, 2013, doi:10.1101/gr.151472.112
...to fully annotate transcriptional regulatory networks in metazoan s. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one...

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