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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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Resource: Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity
- Lingyun Song,
- Zhancheng Zhang,
- Linda L. Grasfeder,
- Alan P. Boyle,
- Paul G. Giresi,
- Bum-Kyu Lee,
- Nathan C. Sheffield,
- Stefan Gräf,
- Mikael Huss,
- Damian Keefe,
- Zheng Liu,
- Darin London,
- Ryan M. McDaniell,
- Yoichiro Shibata,
- Kimberly A. Showers,
- Jeremy M. Simon,
- Teresa Vales,
- Tianyuan Wang,
- Deborah Winter,
- Zhuzhu Zhang,
- Neil D. Clarke,
- Ewan Birney,
- Vishwanath R. Iyer,
- Gregory E. Crawford,
- Jason D. Lieb,
- and Terrence S. Furey
Genome Res. October 2011 21: 1757-1767; Published in Advance July 12, 2011, doi:10.1101/gr.121541.111
...to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined...
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Research: Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations
- Ryne C. Ramaker,
- Andrew A. Hardigan,
- Say-Tar Goh,
- E. Christopher Partridge,
- Barbara Wold,
- Sara J. Cooper,
- and Richard M. Myers
Genome Res. July 2020 30: 939-950; Published in Advance July 2, 2020, doi:10.1101/gr.260463.119
...with an orthogonal data set of 352 nonredundant, in vitro–derived motifs mapped to the within DNase I hypersensitivity footprints to characterize regions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in Hep...
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Research: Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors
- Martin Cusack,
- Hamish W. King,
- Paolo Spingardi,
- Benedikt M. Kessler,
- Robert J. Klose,
- and Skirmantas Kriaucionis
Genome Res. October 2020 30: 1393-1406; Published in Advance September 22, 2020, doi:10.1101/gr.257576.119
...Gs in the are methylated, DNA methylation is absent or reduced in regions bound by transcription factors such as in CpG islands, gene promoters, and distal regulatory elements (Stadler et al. 2011; Hon et al. 2013; Ziller et al. 2013). This observation led to the proposal that DNA methylation may limit transcription...
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Method: Sequential regulatory activity prediction across chromosomes with convolutional neural networks
- David R. Kelley,
- Yakir A. Reshef,
- Maxwell Bileschi,
- David Belanger,
- Cory Y. McLean,
- and Jasper Snoek
Genome Res. May 2018 28: 739-750; Published in Advance March 27, 2018, doi:10.1101/gr.227819.117
...profiles in large mammalian s from DNA sequence alone. By use of convolutional neural networks, this system identifies promoters and distal regulatory elements and synthesizes their content to make effective gene expression predictions. We show that model predictions for the influence of genomic variants...
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Research: Local sequence features that influence AP-1 cis-regulatory activity
- Hemangi G. Chaudhari and
- Barak A. Cohen
Genome Res. February 2018 28: 171-181; Published in Advance January 5, 2018, doi:10.1101/gr.226530.117
...near Activator Protein 1 (AP-1) binding sites that reside in DNase I Hypersensitive Sites (DHS) and regions annotated as Enhancers. In these regions, we found that sequence features directly adjacent to the core motif distinguish high from low activity AP-1 sites. Some nearby features are motifs...
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Method: Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells
- Emily R. Miraldi,
- Maria Pokrovskii,
- Aaron Watters,
- Dayanne M. Castro,
- Nicholas De Veaux,
- Jason A. Hall,
- June-Yong Lee,
- Maria Ciofani,
- Aviv Madar,
- Nick Carriero,
- Dan R. Littman,
- and Richard Bonneau
Genome Res. March 2019 29: 449-463; Published in Advance January 29, 2019, doi:10.1101/gr.238253.118
...-seq, or DNase I hypersensitive sites (DHS) experiment in standard, widely adopted protocols. ATAC-seq is also possible at single-cell resolution (Buenrostro et al. 2015).In the context of TRN inference, chromatin state measurements provide an initial set of putative TF–gene interactions based on evidence of TF...
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Research: Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
- Juan L. Mateo,
- Debbie L.C. van den Berg,
- Maximilian Haeussler,
- Daniela Drechsel,
- Zachary B. Gaber,
- Diogo S. Castro,
- Paul Robson,
- Q. Richard Lu,
- Gregory E. Crawford,
- Paul Flicek,
- Laurence Ettwiller,
- Joachim Wittbrodt,
- François Guillemot,
- and Ben Martynoga
Genome Res. January 2015 25: 41-56; Published in Advance October 7, 2014, doi:10.1101/gr.173435.114
...expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis...
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Research: Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements
- Ofir Hakim,
- Myong-Hee Sung,
- Ty C. Voss,
- Erik Splinter,
- Sam John,
- Peter J. Sabo,
- Robert E. Thurman,
- John A. Stamatoyannopoulos,
- Wouter de Laat,
- and Gordon L. Hager
Genome Res. May 2011 21: 697-706; Published in Advance April 6, 2011, doi:10.1101/gr.111153.110
...genes and thousands ofDHSs are found inproximity of aGR target gene in resting cells, and the interaction network expands further after hormone treatment. We also discovered DNase I hypersensitivity to be the most salient genomic feature of loci interactingwith Lcn2,Arrdc2, andAnxa5. Because chromatin...
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Methods: FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin
- Paul G. Giresi,
- Jonghwan Kim,
- Ryan M. McDaniell,
- Vishwanath R. Iyer,
- and Jason D. Lieb
Genome Res. June 2007 17: 877-885; Published in Advance December 19, 2006, doi:10.1101/gr.5533506
...of regulatory regions in human chromatin. Here, we performed FAIRE in a human foreskin fibroblast cell line and assayed its performance within the genomic regions selected by the ENCODE Project Consortium (2004) . Regions enriched by FAIRE were compared with functional genomic elements such as DNaseI...
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