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PER1/2 transcriptional regulation by multiple upstream signals. Ca2+/cAMP signaling cascade activates CREB by phosphorylation. Activated CREB binds the cAMP response element (CRE) to drive PER1/2 transcription. Other proteins (HSF, heat shock factor; HIF, hypoxia inducible factor; GR, glucocorticoid receptor) recognize and bind other consensus sequences (HSE, heat shock element; HRE, hypoxia response element; GRE, glucocorticoid response element).
