 The PER/TIM heterodimer negatively regulates transcription of "period" ("per") and "timeless" ("tim") genes.Within this negative feedback loop, first the PER/TIM heterodimers form in the cytoplasm, accumulate, and then translocate to the nucleus.The complex then blocks the positive transcription factors clock (CLK) and cycle (CYC), thereby repressing the transcription of "per".