The human PERI1 gene is transcriptionally regulated by multiple signaling pathways

The mammalian period (Per) genes are components of the circadian clock and appear to be regulated via an autoregulatory feedback loop. Here we show th at the human PERI (hPER1) gene is synergistically activated by protein kina ses A and C (PKA, PKC) and cAMP responsive element binding protein. Activat ors and inhibitors of PKA as well as PKC modulate endogenous hPER1 expressi on and kPER1 promoter-driven reporter gene activity in a dose-dependent man ner. Our results suggest that the hPER1 promoter acts as a sensor for multi ple signaling molecules thereby integrating different physiological paramet ers. This regulation of hPER1 appears to be significant for rapid adaptatio n to changing environmental conditions. (C) 2000 Federation of European Bio chemical Societies. Published by Elsevier Science B.V. All rights reserved.