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Quantitative analysis demonstrates most transcription factors require only simple models of specificity

Nature Biotechnology volume 29, pages 480–483 (2011)Cite this article

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Determining the specificity of transcription factors is an important step in understanding regulatory networks and the effects of genetic variations on those networks. To date, attempts to use position weight matrices (PWMs) to assess the DNA-binding specificity of transcription factors from protein binding microarray (PBM) data have suggested that the energetics of transcription factor–DNA recognition fail to follow simple rules. Here we describe a new method for deriving PWMs from PBMs, BEEML-PBM (Binding Energy Estimation by Maximum Likelihood for PBMs). Using this method, we demonstrate that simple PWMs generally do give good approximations of transcription factor specificity, which are reproducible in PBM experiments.

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Figure 1: Plag1 can be modeled well by a single PWM.
Figure 2: A single BEEML-PBM PWM explains the 'secondary motif' phenomenon.

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Acknowledgements

We thank T. Hughes, M. Bulyk and Q. Morris for very helpful comments on the manuscript. We also thank members of the Stormo laboratory for their comments and suggestions throughout the course of this work. This work was supported by National Institutes of Health (NIH) grant R01 HG00249 to G.D.S. and NIH training grant T32 HG00045 to Y.Z.

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  1. Washington University Medical School, St. Louis, Missouri, USA

    Yue Zhao & Gary D Stormo

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  1. Yue Zhao
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  2. Gary D Stormo
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Correspondence to Gary D Stormo.

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Zhao, Y., Stormo, G. Quantitative analysis demonstrates most transcription factors require only simple models of specificity. Nat Biotechnol 29, 480–483 (2011). https://doi.org/10.1038/nbt.1893

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