MYBS: a comprehensive web server for mining transcription factor binding sites in yeast

Abstract

Correct interactions between transcription factors (TFs) and their binding sites (TFBSs) are of central importance to gene regulation. Recently developed chromatin-immunoprecipitation DNA chip (ChIP-chip) techniques and the phylogenetic footprinting method provide ways to identify TFBSs with high precision. In this study, we constructed a user-friendly interactive platform for dynamic binding site mapping using ChIP-chip data and phylogenetic footprinting as two filters. MYBS (Mining Yeast Binding Sites) is a comprehensive web server that integrates an array of both experimentally verified and predicted position weight matrixes (PWMs) from eleven databases, including 481 binding motif consensus sequences and 71 PWMs that correspond to 183 TFs. MYBS users can search within this platform for motif occurrences (possible binding sites) in the promoters of genes of interest via simple motif or gene queries in conjunction with the above two filters. In addition, MYBS enables users to visualize in parallel the potential regulators for a given set of genes, a feature useful for finding potential regulatory associations between TFs. MYBS also allows users to identify target gene sets of each TF pair, which could be used as a starting point for further explorations of TF combinatorial regulation. MYBS is available at http://cg1.iis.sinica.edu.tw/~mybs/.

Figure 1.

Users can study the relationships between motifs, TFs and genes in the following ways: For a query by motif consensus, MYBS will report the TFs whose binding consensus match well to it (upper left); the user may also obtain possible motif consensuses bound by specific TFs (upper right), or search for potential regulators of a gene (lower right). Sequence information can be visualized in detail (lower left). Note that there is a multiple-to-multiple relationship between TFs and motifs, as well as between motifs and genes.

Figure 2.

Distributions of ChIP-chip P-values and the degree of conservation for 101 experimentally verified TFBSs in S. cerevisiae. (A) Comparison of ChIP-chip P-values of 101 TFBSs that were identified and were not identified by MYBS. The ChIP-chip P-values are shown in logarithmic scales. (B) The distribution of these TFBSs conserved in other seven species. The y-axis represents the number of orthologous genes in other yeast species. Each bar represents an experimentally verified TFBS, where the black bar and the white bar represent the number of orthologous genes with and without the conserved TFBS, respectively.

Figure 3.

An example of a regulatory associations contact map. A regulatory association search using MYBS is performed on 111 intron-containing genes sensitive to Dep1p loss. The search provides a contact map of the genes against all TFs, and the map is sorted according to the number of regulatory interactions; in the map, a red block represents a regulatory relationship between a gene and a TF under user-defined criteria and a black block indicates the absence of regulatory relationship. According to the results, 69 of the 111 genes might be jointly regulated by FHL1 and RAP1.