Figure 7 | British Journal of Cancer

Figure 7

From: Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2

Figure 7

Schematic illustration of the molecular anatomy of the endosialin promoter and regulatory pathways induced by hypoxia and cell density. Distal part of the promoter contains adjacent hypoxia-responsive element (HRE) and ETS transcription factor-binding site (EBS) element and transmits hypoxic signalling through hypoxia-inducible factor (HIF)-2 directly binding to DNA and cooperating with Ets-1. Proximal part of the promoter contains two EBS elements (but not HRE) and hypoxia signalling is mediated by HIF-2 through Ets-1 and two EBS elements. High cell density contributes to endosialin activation by means of SP1-binding sites in the proximal promoter and partially feeds the hypoxic pathway by pericellular hypoxia. Moreover, hypoxia might influence activation of endosialin indirectly through HIF-1 that upregulates expression of Ets-1, which in turn upregulates expression of SP1. On the basis of this model, hypoxia and density cross-talk to induce endosialin transcription.

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