text: * Clock – The clock gene in Drosophila encodes for the CLOCK protein and forms a heterodimer with the protein CYCLE in order to control the main oscillating activity of the circadian clock. The heterodimer binds to the E-box promoter region of both per and tim which causes activation of their respective gene expression. Once protein levels for both PER and TIM have reached a critical point, they too dimerize and interact with the CLOCK-CYCLE heterodimer to prevent it from binding to the E-Box and activating transcription. This negative feedback loop is essential for the functioning and timing of the circadian clock.
  * Cycle – the cycle gene encodes for the CYCLE protein to form a heterodimer with the protein CLOCK. The heterodimer creates a transcription-translation feedback loop that controls the levels of both the PER and TIM gene. This feedback loop has been shown to be imperative for both the functioning and timing of the circadian clock in Drosophila. For more information, refer to Clock.
  * Per – The per gene is a clock gene that encodes for the PER protein in Drosophila. The protein levels and transcription rates of PER demonstrate robust circadian rhythms that peak around CT 16. It creates a heterodimer with TIM to control the circadian rhythm. The heterodimer enters the nucleus in order to inhibit the CLOCK-CYCLE heterodimer which acts as a transcriptional activator for per and tim. This results in an inhibition of the transcription factors of per and tim thereby lowering the respective mRNA levels and protein levels. For more information, refer to Clock.
  * Timeless – The tim gene encodes for the TIM protein that is critical in circadian regulation in Drosophila. Its protein levels and transcription rates demonstrate a circadian oscillation that peaks at around CT 16. TIM binds to the PER protein to create a heterodimer whose transcription-translation feedback loop controls the periodicity and phase of the circadian rhythms. For more information, refer to Period and Clock.