Spitz, F. & Furlong, E. E. M. Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13, 613â626 (2012).
Kelly, T. K. et al. Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules. Genome Res. 22, 2497â2506 (2012).
Krebs, A. R. et al. Genome-wide single-molecule footprinting reveals high RNA polymerase II turnover at paused promoters. Mol. Cell 67, 411â422 (2017).
Vierstra, J. et al. Global reference mapping of human transcription factor footprints. Nature 583, 729â736 (2020).
Wunderlich, Z. & Mirny, L. A. Different gene regulation strategies revealed by analysis of binding motifs. Trends Genet. 25, 434â440 (2009).
Giniger, E. & Ptashne, M. Cooperative DNA binding of the yeast transcriptional activator GAL4. Proc. Natl Acad. Sci. USA 85, 382â386 (1988).
Pettersson, M. & Schaffner, W. Synergistic activation of transcription by multiple binding sites for NF-kappa B even in absence of co-operative factor binding to DNA. J. Mol. Biol. 214, 373â380 (1990).
Thanos, D. & Maniatis, T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 83, 1091â1100 (1995).
Mirny, L. A. Nucleosome-mediated cooperativity between transcription factors. Proc. Natl Acad. Sci. USA 107, 22534â22539 (2010).
Biddie, S. C. et al. Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol. Cell 43, 145â155 (2011).
Fryer, C. J. & Archer, T. K. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature 393, 88â91 (1998).
Herschlag, D. & Johnson, F. B. Synergism in transcriptional activation: a kinetic view. Genes Dev. 7, 173â179 (1993).
Martinez-Corral, R. et al. Transcriptional kinetic synergy: a complex landscape revealed by integrating modeling and synthetic biology. Cell Syst. 14, 324â339 (2023).
Shipony, Z. et al. Long-range single-molecule mapping of chromatin accessibility in eukaryotes. Nat. Methods 17, 319â327 (2020).
Stergachis, A. B., Debo, B. M., Haugen, E., Churchman, L. S. & Stamatoyannopoulos, J. A. Single-molecule regulatory architectures captured by chromatin fiber sequencing. Science 368, 1449â1454 (2020).
Sönmezer, C. et al. Molecular co-occupancy identifies transcription factor binding cooperativity in vivo. Mol. Cell 81, 255â267 (2021).
Levo, M. et al. Systematic investigation of transcription factor activity in the context of chromatin using massively parallel binding and expression assays. Mol. Cell 65, 604â617 (2017).
Bintu, L. et al. Transcriptional regulation by the numbers: models. Curr. Opin. Genet. Dev. 15, 116â124 (2005).
Gossen, M. et al. Transcriptional activation by tetracyclines in mammalian cells. Science 268, 1766â1769 (1995).
Vaisvila, R. et al. Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Genome Res. 31, 1280â1289 (2021).
Ackers, G. K., Johnson, A. D. & Shea, M. A. Quantitative model for gene regulation by lambda phage repressor. Proc. Natl Acad. Sci. USA 79, 1129â1133 (1982).
Kim, H. D. & OâShea, E. K. A quantitative model of transcription factor-activated gene expression. Nat. Struct. Mol. Biol. 15, 1192â1198 (2008).
Neely, K. E. et al. Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol. Cell 4, 649â655 (1999).
Yudkovsky, N., Logie, C., Hahn, S. & Peterson, C. L. Recruitment of the SWI/SNF chromatin remodeling complex by transcriptional activators. Genes Dev. 13, 2369â2374 (1999).
Neely, K. E., Hassan, A. H., Brown, C. E., Howe, L. & Workman, J. L. Transcription activator interactions with multiple SWI/SNF subunits. Mol. Cell. Biol. 22, 1615â1625 (2002).
Papillon, J. P. N. et al. Discovery of orally active inhibitors of Brahma homolog (BRM)/SMARCA2 ATPase activity for the treatment of Brahma related gene 1 (BRG1)/SMARCA4-mutant cancers. J. Med. Chem. 61, 10155â10172 (2018).
Martin, B. J. E. et al. Global identification of SWI/SNF targets reveals compensation by EP400. Cell https://doi.org/10.1016/j.cell.2023.10.006 (2023).
Kundu, T. K. et al. Activator-dependent transcription from chromatin in vitro involving targeted histone acetylation by p300. Mol. Cell 6, 551â561 (2000).
Alerasool, N., Leng, H., Lin, Z.-Y., Gingras, A.-C. & Taipale, M. Identification and functional characterization of transcriptional activators in human cells. Mol. Cell 82, 677â695 (2022).
Rada-Iglesias, A. et al. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279â283 (2011).
Brower-Toland, B. et al. Specific contributions of histone tails and their acetylation to the mechanical stability of nucleosomes. J. Mol. Biol. 346, 135â146 (2005).
Lasko, L. M. et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature 550, 128â132 (2017).
Raj, A., Peskin, C. S., Tranchina, D., Vargas, D. Y. & Tyagi, S. Stochastic mRNA synthesis in mammalian cells. PLoS Biol. 4, e309 (2006).
Suter, D. M. et al. Mammalian genes are transcribed with widely different bursting kinetics. Science 332, 472â474 (2011).
Chong, S., Chen, C., Ge, H. & Xie, X. S. Mechanism of transcriptional bursting in bacteria. Cell 158, 314â326 (2014).
Xiao, J. Y., Hafner, A. & Boettiger, A. N. How subtle changes in 3D structure can create large changes in transcription. Elife 10, e64320 (2021).
Zuin, J. et al. Nonlinear control of transcription through enhancerâpromoter interactions. Nature 604, 571â577 (2022).
Gossen, M. & Bujard, H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547â5551 (1992).
Kessler, D. S., Veals, S. A., Fu, X. Y. & Levy, D. E. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev. 4, 1753â1765 (1990).
Lazear, H. M., Schoggins, J. W. & Diamond, M. S. Shared and distinct functions of type I and type III interferons. Immunity 50, 907â923 (2019).
Platanitis, E. et al. A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription. Nat. Commun. 10, 2921 (2019).
Rengachari, S. et al. Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function. Proc. Natl Acad. Sci. USA 115, E601âE609 (2018).
Bluyssen, H. A. & Levy, D. E. Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA. J. Biol. Chem. 272, 4600â4605 (1997).
Patel, M. C. et al. BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes. Mol. Cell. Biol. 33, 2497â2507 (2013).
Cui, K. et al. The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming. Mol. Cell. Biol. 24, 4476â4486 (2004).
Manry, J. et al. Evolutionary genetic dissection of human interferons. J. Exp. Med. 208, 2747â2759 (2011).
Krause, C. D. & Pestka, S. Cut, copy, move, delete: the study of human interferon genes reveal multiple mechanisms underlying their evolution in amniotes. Cytokine 76, 480â495 (2015).
Arimoto, K.-I., Miyauchi, S., Stoner, S. A., Fan, J.-B. & Zhang, D.-E. Negative regulation of type I IFN signaling. J. Leukoc. Biol. https://doi.org/10.1002/JLB.2MIR0817-342R (2018).
Mostafavi, S. et al. Parsing the interferon transcriptional network and its disease associations. Cell 164, 564â578 (2016).
Dogan, N. et al. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility. Epigenetics Chromatin 8, 16 (2015).
Corces, M. R. et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat. Genet. 48, 1193â1203 (2016).
Weirauch, M. T. et al. Evaluation of methods for modeling transcription factor sequence specificity. Nat. Biotechnol. 31, 126â134 (2013).
Lee, D. Y., Hayes, J. J., Pruss, D. & Wolffe, A. P. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72, 73â84 (1993).
Struhl, K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 12, 599â606 (1998).
Narita, T. et al. Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. Mol. Cell 81, 2166â2182 (2021).
Ferrie, J. J. et al. p300 is an obligate integrator of combinatorial transcription factor inputs. Mol. Cell 84, 234â243.e4 (2024).
Kornberg, R. D. & Lorch, Y. Irresistible force meets immovable object: transcription and the nucleosome. Cell 67, 833â836 (1991).
Boeger, H. Kinetic proofreading. Annu. Rev. Biochem. 91, 423â447 (2022).
Wong, F. & Gunawardena, J. Gene regulation in and out of equilibrium. Annu. Rev. Biophys. 49, 199â226 (2020).
Shelansky, R. & Boeger, H. Nucleosomal proofreading of activator-promoter interactions. Proc. Natl Acad. Sci. USA 117, 2456â2461 (2020).
Mahdavi, S., Salmon, G. L., Daghlian, P., Garcia, H. G. & Phillips, R. Flexibility and sensitivity in gene regulation out of equilibrium. Preprint at bioRxiv https://doi.org/10.1101/2023.04.11.536490 (2023).
Guharajan, S., Parisutham, V. & Brewster, R. C. Probing the dependence of transcription factor regulatory modes on promoter features. Preprint at bioRxiv https://doi.org/10.1101/2024.05.30.596689 (2024).
Vaisvila, R. et al. Discovery of cytosine deaminases enables base-resolution methylome mapping using a single enzyme. Mol. Cell 84, 854â866 (2024).
He, R. et al. Human transcription factor combinations mapped by footprinting with deaminase. Preprint at bioRxiv https://doi.org/10.1101/2024.06.14.599019 (2024).
Policarpi, C., Munafò, M., Tsagkris, S., Carlini, V. & Hackett, J. A. Systematic epigenome editing captures the context-dependent instructive function of chromatin modifications. Nat. Genet. https://doi.org/10.1038/s41588-024-01706-w (2024).
DelRosso, N. et al. Large-scale mapping and mutagenesis of human transcriptional effector domains. Nature 616, 365â372 (2023).
Durrant, M. G. et al. Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome. Nat. Biotechnol. 41, 488â499 (2023).
Tycko, J. et al. High-throughput discovery and characterization of human transcriptional effectors. Cell 183, 2020â2035 (2020).
Iurlaro, M. et al. Mammalian SWI/SNF continuously restores local accessibility to chromatin. Nat. Genet. 53, 279â287 (2021).
Weinert, B. T. et al. Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300 acetylome. Cell 174, 231â244 (2018).
Teague, B. Cytoflow: a Python toolbox for flow cytometry. Preprint at bioRxiv https://doi.org/10.1101/2022.07.22.501078 (2022).
Pedersen, B. S., Eyring, K., De, S., Yang, I. V. & Schwartz, D. A. Fast and accurate alignment of long bisulfite-seq reads. Preprint at https://arxiv.org/abs/1401.1129 (2014).
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261â272 (2020).
Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959â962 (2017).
Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24â26 (2011).
Schep, A. N., Wu, B., Buenrostro, J. D. & Greenleaf, W. J. chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat. Methods 14, 975â978 (2017).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Marinov, G. K. ChIP-seq for the identification of functional elements in the human genome. Methods Mol. Biol. 1543, 3â18 (2017).
Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X. S. Identifying ChIP-seq enrichment using MACS. Nat. Protoc. 7, 1728â1740 (2012).
Marinov, G. K. Identification of candidate functional elements in the genome from ChIP-seq data. Methods Mol. Biol. 1543, 19â43 (2017).
Doughty, B. GreenleafLab/synthetic_enhancer_footprinting_additional_materials: SMF Paper Files. Zenodo https://doi.org/10.5281/zenodo.13841007 (2024).
Doughty, B. GreenleafLab/amplicon-smf: amplicon-smf v1.0.0. Zenodo https://doi.org/10.5281/zenodo.13840888 (2024).