Hu and Gallo BMC Genomics 2010, 11:49 http://www.biomedcentral.com/1471-2164/11/49 Page 8 of 15 Figure 3 Conservation of identified HNF3 and HNF4ALPHA binding sites in human and mouse APOA1 genes. Both schematic and sequence alignments for the predicted HNF3 and HNF4ALPHA binding sites between human and mouse promoter sequences are depicted. In the sequence alignment the core motifs are shown in upper case letters and the distances between adjacent binding sites are shown in brackets. Also shown are the locations of each binding site in relation to the transcriptional starting site. FAC1, when serving as the internal TF, is restricted to the two related tissue types, and that SPZ1, a bHLH-Zip protein, has an important role in testis [29,30]. The rest have more diversified roles for coordinating network TFs in controlling tissue gene expression. It is interesting to note that no single TFs serve as the central hub for tissue-type TF-TF interaction networks from liver tissue. However, we observed that 6 of 7 tissue-type TF-TF interaction networks had at least one known liver-specific TF serving as the internal TF as shown in Figure 6b. To investigate if this distribution pattern of liver-specific TFs in the TF-TF interaction networks had any biological meaning, we randomly sampled TFs from the 214 PWMs to build TF-TF net- works, each having the same size and order as the real TF-TF interaction networks. The simulated TF-TF Figure 4 Hierarchical clustering over tissue TF pairs from the 79 human tissues. The distance matrix was built using the “binary” method, and hierarchical clustering was performed using the “complete” agglomeration method. Arrows and numbers indicate the selected tissue groups for further analysis.