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Ab Initio Prediction of Transcription Factor Targets Using Structural Knowledge

Figure 6

Inferring the Function and Activity of Zinc Finger Transcription Factors in D. melanogaster

(A) Similar gene annotation enrichment among the putative target sets of 29 transcription factors in D. melanogaster. Blue cells correspond to significant overabundance of a GO term (row) among the predicted targets of a protein (column), using a hyper-geometric test. The binding sites of most factors show enrichment in at least one GO term. For some of the regulators, the enriched GO terms match prior biological knowledge. For example, the putative targets of Glass (gl) were found to be enriched with terms related to photoreceptor cell development (red circle 1). Similarly, the putative targets of Buttonhead (btd) and Sp1 were enriched with developmental terms such as neurogenesis, development, and organogenesis (red circle 2). Closely related GO annotations are not shown; see Figure S4 for full results.

(B) Deducing the activity of the 29 transcription factors using gene expression patterns. Expression data from early (0–12 h) embryogenesis [20] and data from the entire Drosophila life cycle [21] are used to test whether the putative direct targets of a regulator are expressed differently than the rest of the genes in a given experiment. Red cells correspond to significant enrichment of overexpressed targets using a Kolmogorov-Smirnov test, while green cells correspond to enrichment of underexpressed targets. For most of the regulators the analysis resulted in at least one significant embryogenesis experiment, suggesting an active role in early developmental stages (above). Similar results were obtained using the full life cycle gene expression data (below).

Figure 6

doi: https://doi.org/10.1371/journal.pcbi.0010001.g006