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Figure 3 | BMC Systems Biology

Figure 3

From: Hypoxia-dependent sequestration of an oxygen sensor by a widespread structural motif can shape the hypoxic response - a predictive kinetic model

Figure 3

Signal/response curves in Skeleton Model 1. A. Increasing FIH activity shifts non-CAD-hydroxylated HIFα to lower oxygen tensions. Total HIFα (black bold line) and HIFα that is not CAD-hydroxylated (coloured fine lines) are shown as functions of oxygen. Parameters used were K ^ D P = K ^ D F = 1 , k ´ c a t P P ^ t o t = k ´ c a t F H F ^ t o t = 100 . In this example, FIH activity was increased by lowering its KM for oxygen relative to PHD's KM for oxygen, however any change in parameters that leads to higher FIH activity gives similar results (data not shown). The green curve (α = 1) represents the case where all kinetic parameters for FIH and PHD are identical. B. Activation status of hypoxia-response elements (HREs). Probabilities for an HRE to be bound by either HIFα that is not CAD-hydroxylated (green solid curve), by CAD-hydroxylated HIFα (red dotted curve) or either form of HIFα (bold black curve) under the assumption that all forms of HIF bind with identical affinity to the HRE( K ^ D H R E = 0.3 ). We propose the existence of a novel set of HIF target genes, which are transcriptionally activated by CAD-hydroxylated HIFα (CADOH-dependent genes). The regimes of differential gene expression are indicated by shading (an arbitrary gene activation threshold was introduced at 20% HRE occupancy). Parameters used were as in A, with α = 0.33[30].

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