Bayesian network analysis of targeting interactions in chromatin

  1. Bas van Steensel1,3,4,
  2. Ulrich Braunschweig1,3,
  3. Guillaume J. Filion1,
  4. Menzies Chen2,
  5. Joke G. van Bemmel1 and
  6. Trey Ideker2,4
  1. 1 Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands;
  2. 2 Departments of Medicine and Bioengineering, University of California at San Diego, La Jolla, California 92093-0688, USA
    1. 3 These authors contributed equally to this work.

    Abstract

    In eukaryotes, many chromatin proteins together regulate gene expression. Chromatin proteins often direct the genomic binding pattern of other chromatin proteins, for example, by recruitment or competition mechanisms. The network of such targeting interactions in chromatin is complex and still poorly understood. Based on genome-wide binding maps, we constructed a Bayesian network model of the targeting interactions among a broad set of 43 chromatin components in Drosophila cells. This model predicts many novel functional relationships. For example, we found that the homologous proteins HP1 and HP1C each target the heterochromatin protein HP3 to distinct sets of genes in a competitive manner. We also discovered a central role for the remodeling factor Brahma in the targeting of several DNA-binding factors, including GAGA factor, JRA, and SU(VAR)3-7. Our network model provides a global view of the targeting interplay among dozens of chromatin components.

    Footnotes

    • 4 Corresponding authors.

      E-mail b.v.steensel{at}nki.nl; fax 31-20-6691383.

      E-mail trey{at}bioeng.ucsd.edu; fax (858) 822-4246.

    • [Supplemental material is available online at http://www.genome.org. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE15807.]

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.098822.109.

      • Received July 27, 2009.
      • Accepted November 4, 2009.
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