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8Bioinformatics Tools for Modeling Transcription FactorTarget Genes and Epigenetic ChangesRamana V. DavuluriSummaryThe combinatorial control of gene regulatory switches involves both transcription factor (TF)complexes and associated epigenetic modifications to the chromatin template. The novel highthroughputtechnologies, such as Chromatin ImmunoPrecipitation ChIP-chip, have enabledgenome-wide in vivo identification of TF target regulatory regions and related epigenetic modifications,which led to the view of highly dynamic TF–DNA interactions in activated or repressedpromoters. Consequently, modeling and elucidating the combinatorial interaction of TFs and correspondingcis-regulatory modules in target promoters is of paramount interest. An estimated 5% of thegenes in mammalian genomes code for TF proteins, and computational modeling of cis-regulatorylogic would rapidly increase the pace of experimental confirmation of TF target promoters at thebench. The purpose of this chapter is to discuss the use of different bioinformatics tools for predictingthe target genes of TFs of interest in mammalian genomes, and the application of these methodsin the analysis of ChIP-chip experimental data. The author describes most commonly useddatabases and prediction programs that are available on the World Wide Web and demonstrate theuse of some of these programs by an example. A list of these programs is provided along with theirweb Uniform Resource Locator (URLs) and guidelines for successful application are suggested.Key Words: Cis-regulatory logic; computational modeling; CpG island; target promoter;transcriptional module; ChIP-chip.1. IntroductionTranscriptional regulation of protein-coding genes involves a number of differentlevels of organization in the cell nucleus. The transcription machinery isresponsible for the decoding and expression of genes in a regulatory networkmade up of various coregulatory complexes that are interconnected to controlRNA synthesis from a given promoter (1). The key players of the transcriptionalregulation are the transcription factors (TFs) that form complexes with otherFrom: Methods in Molecular Biology, vol. 408: Gene Function AnalysisEdited by: M. Ochs © Humana Press Inc., Totowa, NJ129