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A PERIOD inhibitor buffer introduces a delay mechanism for CLK/CYC‐activated transcription
Author(s) -
Weber Frank,
Kay Steve A
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01269-9
Subject(s) - timeless , transcription (linguistics) , transcription factor , circadian clock , biology , microbiology and biotechnology , circadian rhythm , gene , genetics , endocrinology , linguistics , philosophy
We investigated the functions of clock genes period ( per ) and timeless ( tim ) in establishing negative feedback on circadian transcription factors clock / cycle ( Clk / cyc ) in Drosophila . We show that PER protein persists for several hours after rapid degradation of TIM in the morning. We observed in cell culture that isolated PER inhibits CLK/CYC‐activated transcription in the absence of TIM and we further demonstrated for the first time in vivo that PER accumulation in a tim loss‐of‐function mutant background causes efficient inhibition of CLK/CYC‐dependent transcription. These results identify PER to be the main inhibitor for CLK/CYC and they suggest a delay mechanism during early morning, when PER protein, after degradation of TIM, forms an inhibitor buffer for CLK/CYC that attenuates the restart of the next cycle of CLK/CYC‐activated transcription. While TIM likely enhances the inhibition of CLK/CYC by PER in the dark, our results suggest a reduction of PER‐mediated inhibition by TIM in light.