YAP binds to and induces genes important for ES cell functions. (A) An enrichment network linking YAP1-bound genes to gene sets regulated in ES cells. YAP1-bound genes (hollow node with black ring) were derived from ChIP-seq analysis of YAP in undifferentiated ES cells, and were compared against all other concepts available in the MCM in Oncomine for significant overlap. Each node represents one molecular concept or gene set with node size proportional to the number of genes. Each edge represents a statistically significant overlap (P < 1 × 10−10) of genes in the two linked nodes. Significance of overlap between two concepts was determined by Fisher's exact test comparing the chance and expected overlap (Rhodes et al. 2007). The odds ratio and P-value of such tests are shown in the table. The P-values for pairs between YAP and all concepts in this network are <3.8 × 10−34 (Supplemental Table S3). (B) YAP binds preferentially to gene promoters containing TEAD sites. The intensity of YAP binding as determined by the number of sequence hits is grouped and plotted on the X-axis. The Y-axis indicates the percentage of genes containing TEAD sites in a given intensity group. The data indicate a positive correlation between the YAP-binding intensity and the presence of TEAD sites (R = 0.92 for control mES cells [light-gray bars] and R = 0.66 for differentiated mES cells [dark-gray bars]). (C) YAP regulates a large set of ES cell important genes. mRNAs were isolated from undifferentiated, differentiated, YAP-5SA-expressing, and YAP knockdown ES cells. Expression of YAP ChIP-positive genes were determined by quantitative RT–PCR. The top panel shows gene expression between control and differentiated ES cells. The middle panel shows expression of corresponding genes in YAP knockdown cells. The bottom panel shows gene expression in YAP-5SA ES cells under differentiation conditions. Quantitative PCR data were normalized to GAPDH control then scaled proportionally in the Y-axis. Samples to the left of the dashed line follow the scale on the left, while samples to the right of the dashed lines follow the scale on the right Y-axis, respectively.