3.3. Promoter Analysis
The result of the promoter analysis (see Section 2.2), for which a complex workflow has been composed (Figure 5), comprises enriched TF-binding motifs for each cluster of up- and down-regulated genes. Table 2 lists the transcription factors that were mapped to the identified enriched motifs. Down-regulated genes of cluster 3 (liver) gave 15 potential TFs, and up-regulated genes from the same cluster revealed 17 identified potential TFs. Running the same workflow in parallel for the up- and down-regulated genes of cluster 4 (lung) resulted in the identification of 55 (down) and 68 (up) potential transcription factors. It may be interesting to note that while there is a considerable overlap among the potential regulators of up- and down-regulated genes in the lung (24), up- and down-regulated genes in the liver have no single TF in common; however, these TF lists are also considerably shorter. The up-regulated liver and lung genes share 4 TFs (Egr1, Egr2, Nr2f2/COUP-TF2, Zscan4f); one of them (Egr1) is a known immediate-early response gene, activated by extracellular signals and mediating mitogenic responses [29].
Figure 5  Schematic overview of the workflow “Enriched upstream analysis (TRANSFAC® and TRANSPATH®)” with input parameters (green), incorporated and linked (arrows) methods (blue), input/output data (yellow) and additive Javascripts (grey text). See Supplementary Figure SF1 for high-resolution version.
microarrays-04-00270-t002_Table 2 Table 2  Table of potential TFs involved in the regulation of the following gene sets: cluster 3 (down-reg. genes in liver), cluster 4 (down-reg. genes in lung), cluster 3 (up-reg. genes in liver) and cluster 4 (up-reg. genes in lung). Underlined are those 4 TFs that are common to the two up-regulated gene sets (liver and lung), two of which appearing in the down-regulated lung set as well.

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