Distribution of HIF-binding sites. The position of HIF-1 and HIF-2-binding sites with respect to the nearest TSS was plotted as a frequency distribution using (A) 5-kb windows and (B) 100-bp windows. Frequency distribution of the nearest-neighbor distance between (C) HIF-1-binding gene loci, (D) HIF-2-binding gene loci, and (E) HIF-regulated gene loci. In each case, the frequency distribution of nearest-neighbor distances for an equal number of randomly selected control gene loci is shown for comparison. (F) The Ingenuity Systems Inc (IPA Version 8.8-3204) software tool was used to examine the HIF-1 and HIF-2-binding loci for functional pathways. Canonical pathways statistically over-represented among HIF-binding loci are shown together with the respective −log₁₀ (P value) for each isoform.