Fig. 3.

Model that questions the molecular significance of the two HIF-1α TAD and the impact of the oxygen sensor FIH on the intra-tumor location of gene expression as a function of the oxygen gradient. aUpper panel: If the two HIF-1α TAD are functionally different they would target different genes. In green are represented the potential N-TAD-only target genes while in blue are represented the potential C-TAD sensitive genes. Lower panel: By targeting specifically the C-TAD, FIH would inhibit only a subset of HIF-dependent genes. Consequently, FIH would not be a pure inhibitor but rather a switch between two categories of HIF spectrum genes. b In accordance with our working model, overexpression of FIH should delocalize C-TAD sensitive genes (blue dotted line) to highly hypoxic areas. In contrast FIH inhibition by siRNA should delocalize C-TAD sensitive genes to moderately hypoxic areas in the vicinity of blood vessels (lower panel). In parallel, N-TAD only genes (green dotted line) should not be sensitive to modulation of FIH activity