A circadian clock gene, PER2, activates HIF‐1 as an effector molecule for recruitment of HIF‐1α to promoter regions of its downstream genes

Forced expression of PER2 enhanced HIF-1 activity without altering HIF-1α levels.

• PER2 acts as an effector protein that helps recruit HIF-1α to its target DNA sequence, the hypoxia-response element (HRE).
• The interaction between PER2 and HIF-1α promotes HIF-1 activity, specifically in the context of the vascular endothelial growth factor (VEGF) promoter.
• The activation of HIF-1 by PER2 occurs only when HIF-1α is unhydroxylated at asparagine residue 803, indicating a specific regulatory mechanism.
• The strength of the PER2-HIF-1α interaction does not change based on the hydroxylation status of HIF-1α N803.

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