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Regulating the Regulators: Modulators of Transcription Factor Activity

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Computational Biology of Transcription Factor Binding

Part of the book series: Methods in Molecular Biology ((MIMB,volume 674))

Abstract

Gene transcription is largely regulated by DNA-binding transcription factors (TFs). However, the TF activity itself is modulated via, among other things, post-translational modifications (PTMs) by specific modification enzymes in response to cellular stimuli. TF-PTMs thus serve as “molecular switchboards” that map upstream signaling events to the downstream transcriptional events. An important long-term goal is to obtain a genome-wide map of “regulatory triplets” consisting of a TF, target gene, and a modulator gene that specifically modulates the regulation of the target gene by the TF. A variety of genome-wide data sets can be exploited by computational methods to obtain a rough map of regulatory triplets, which can guide directed experiments. However, a prerequisite to developing such computational tools is a systematic catalog of known instances of regulatory triplets. We first describe PTM-Switchboard, a recent database that stores triplets of genes such that the ability of one gene (the TF) to regulate a target gene is dependent on one or more PTMs catalyzed by a third gene, the modifying enzyme. We also review current computational approaches to infer regulatory triplets from genome-wide data sets and conclude with a discussion of potential future research. PTM-Switchboard is accessible at http://cagr.pcbi.upenn.edu/PTMswitchboard/

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Acknowledgments

This work was supported by The National Institutes of Health grants R01GM085226 (MH, SH), and T32HG000046 (LE).

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Authors and Affiliations

  1. Department of Genetics, Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA, USA

    Logan Everett, Matthew Hansen & Sridhar Hannenhalli

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  1. Logan Everett
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  2. Matthew Hansen
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  3. Sridhar Hannenhalli
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Corresponding author

Correspondence to Sridhar Hannenhalli .

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Editors and Affiliations

  1. , Department of Statistics, University of Nebraska-Lincoln, Vine Street 1901, Lincoln, 68588-0665, Nebraska, USA

    Istvan Ladunga

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Everett, L., Hansen, M., Hannenhalli, S. (2010). Regulating the Regulators: Modulators of Transcription Factor Activity. In: Ladunga, I. (eds) Computational Biology of Transcription Factor Binding. Methods in Molecular Biology, vol 674. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-854-6_19

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  • DOI: https://doi.org/10.1007/978-1-60761-854-6_19

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