skip to main content
10.1145/1854776.1854827acmconferencesArticle/Chapter ViewAbstractPublication PagesbcbConference Proceedingsconference-collections
research-article

Modeling the competitive effects of nucleosomes on transcription factors binding

Published: 02 August 2010 Publication History

Abstract

Transcription factor-DNA interactions play a central role in transcriptional control. These bindings are stochastic processes and regulated by the nucleosomes in vivo. However, most of the current models tend to neglect nucleosomes and regard bindings as discrete binary events rather than continuous ones. To address the issues, we proposed a model by integrating TF bindings to nucleosomal and naked DNA in a quantitative manner. We evaluated the predictive ability of the model using the experimental TF binding profiles and functional DNA binding sites. The evaluation results show that incorporating nucleosome can greatly improve the prediction accuracy of in vivo binding for many TFs in yeast over the models disregarding the nucleosomes.

References

[1]
T. J. Richmond, and C. A. Davey. 2003. The structure of DNA in the nucleosome core. NATURE. 423, 6936 (May. 2003), 145--150.
[2]
J. D. Anderson, P. T. Lowary, and J. Widom. 2001. Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites. Journal of molecular biology. 307, 4 (Apr. 2001), 977--985.
[3]
J. A. Granek, and N. D. Clarke. 2005. Explicit equilibrium modeling of transcription-factor binding and gene regulation. Genome Biology. 6, 10 (2005)
[4]
H. G. Roider, A. Kanhere, T. Manke et al. 2007. Predicting transcription factor affinities to DNA from a biophysical model. Bioinformatics. 23, 2 (Jan. 2007), 134--141.
[5]
X. Liu, C. K. Lee, J. A. Granek et al. 2006. Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection. Genome Research. 16, 12 (Dec. 2006), 1517--1528.
[6]
T. Raveh-Sadka, M. Levo, and E. Segal. 2009. Incorporating Nucleosomes into Thermodynamic Models of Transcription Regulation. Genome Research. (2009)
[7]
L. Narlikar, R. Gordan, and A. J. Hartemink. 2007. A nucleosome-guided map of transcription factor binding sites in yeast. Plos Computational Biology. 3, 11 (Nov. 2007), 2199--2208.
[8]
J. Monod, J. Wyman, and J. P. Changeux. 1965. On the nature of allosteric transitions: a plausible model. Journal of molecular biology. 12, (1965), 88--118.
[9]
M. Djordjevic, A. M. Sengupta, and B. I. Shraiman. 2003. A biophysical approach to transcription factor binding site discovery. Genome Research. 13, 11 (Nov. 2003), 2381--2390.
[10]
G. D. Stormo, and D. S. Fields. 1998. Specificity, free energy and information content in protein-DNA interactions. Trends Biochem Sci 3, (1998), 109--113.
[11]
L. A. Mirny. 2009. Nucleosome-mediated cooperativity between transcription factors. 2009arXiv09012905M. (2009)
[12]
C. T. Harbison, D. B. Gordon, T. I. Lee et al. 2004. Transcriptional regulatory code of a eukaryotic genome. NATURE. 431, 7004 (Sep. 2004), 99--104.
[13]
G. Badis, E. T. Chan, H. van Bakel et al. 2008. A Library of Yeast Transcription Factor Motifs Reveals a Widespread Function for Rsc3 in Targeting Nucleosome Exclusion at Promoters. Molecular Cell. 32, 6 (Dec. 2008), 878--887.
[14]
K. D. MacIsaac, T. Wang, D. B. Gordon et al. 2006. An improved map of conserved regulatory sites for Saccharomyces cerevisiae. BMC Bioinformatics. 7, (Mar. 2006)
[15]
N. Kaplan, I. K. Moore, Y. Fondufe-Mittendorf et al. 2009. The DNA-encoded nucleosome organization of a eukaryotic genome. NATURE. 458, 7236 (Mar. 2009), 362-U129.
[16]
T. Whitington, A. C. Perkins, and T. L. Bailey. 2009. High-throughput chromatin information enables accurate tissue-specific prediction of transcription factor binding sites. Nucleic Acids Research. 37, 1 (Jan. 2009), 14--25.
[17]
O. Berg, and P. von Hippel. 1987. Selection of DNA binding sites by regulatory proteins: statistical-mechanical theory and application to operators and promoters. Journal of molecular biology. 193, (1987), 723--750.

Index Terms

  1. Modeling the competitive effects of nucleosomes on transcription factors binding

        Recommendations

        Comments

        Information & Contributors

        Information

        Published In

        cover image ACM Conferences
        BCB '10: Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology
        August 2010
        705 pages
        ISBN:9781450304382
        DOI:10.1145/1854776
        Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

        Sponsors

        Publisher

        Association for Computing Machinery

        New York, NY, United States

        Publication History

        Published: 02 August 2010

        Permissions

        Request permissions for this article.

        Check for updates

        Author Tags

        1. TF-DNA interaction
        2. model
        3. nucleosome

        Qualifiers

        • Research-article

        Funding Sources

        Conference

        BCB'10
        Sponsor:

        Acceptance Rates

        Overall Acceptance Rate 254 of 885 submissions, 29%

        Contributors

        Other Metrics

        Bibliometrics & Citations

        Bibliometrics

        Article Metrics

        • 0
          Total Citations
        • 82
          Total Downloads
        • Downloads (Last 12 months)0
        • Downloads (Last 6 weeks)0
        Reflects downloads up to 20 Feb 2025

        Other Metrics

        Citations

        View Options

        Login options

        View options

        PDF

        View or Download as a PDF file.

        PDF

        eReader

        View online with eReader.

        eReader

        Figures

        Tables

        Media

        Share

        Share

        Share this Publication link

        Share on social media