Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions
Figure 1
Basal gene expression is not sufficient for HIF transactivation.
(A) A list of well-characterized HIF target genes (from ref. 7) present in individual gene expression profiling (microarray) datasets (see B for GEO IDs) were categorized according to their basal (normoxic) expression level into two groups: Null, no detectable basal expression; Significant, detectable basal expression. In addition, for each microarray experiment, HIF-target genes were further classified into those whose expression was significantly induced by hypoxia (ratio hypoxia/normoxia greater than 2.6Sd above the mean) and non-responsive genes. The graph represents the percentage of HIF target genes in each category that were induced by hypoxia. Each pair of joined dots represents the data from a single microarray experiment. Box and whisker plots represent the distribution of values in each category. **: p<0.01 (Wilkoxon matched test) (B) For each of the indicated microarray datasets (GEO identifiers in horizontal axis), we identified all the genes showing a significant basal (normoxic) expression. Then, we classified them according to their response to hypoxia (“Induced” and “notInduced”, see A) and the presence of conserved RCGTG motifs in their regulatory regions (“HBS” and “NoHBS”, respectively). The graph depicts cumulative percentages (vertical axis) of genes in each of the four combinations of the two categories: no conserved HIF binding motifs and no hypoxic induction (blue, NoHBS_notInduced), no conserved HIF binding motifs but hypoxic induction (green, NoHBS_Induced), conserved HIF binding motifs but no hypoxic induction (yellow, HBS_notInduced) and conserved HIF binding sites and hypoxic induction (red, HBS_Induced).