A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery

Depletion of TRAP150 in mice led to low-amplitude, long-period circadian rhythms.

• The circadian clock in mammals relies on a negative feedback loop involving the CLOCK-BMAL1 complex and its inhibitors, PERIOD and CRYPTOCHROME.
• Mouse BMAL1 complexes were found to include TRAP150, which acts as a selective coactivator for CLOCK-BMAL1.
• TRAP150 enhances CLOCK-BMAL1's ability to bind to target genes and connects it to the transcriptional machinery.
• The discovery of TRAP150's role indicates it functions as a positive clock element within the circadian rhythm mechanism.
• This suggests that TRAP150 may facilitate the timing of CLOCK-BMAL1 reactivation after the turnover of PERIOD and CRYPTOCHROME proteins.

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