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. Author manuscript; available in PMC: 2015 Mar 1.
Published in final edited form as: Prog Retin Eye Res. 2013 Dec 12;0:58–76. doi: 10.1016/j.preteyeres.2013.12.001

Figure 2. The molecular mechanism generating the circadian oscillation is composed of two feedback loops.

Figure 2

In the positive feedback loop the transcription factors Bmal1 and Clock activate the transcription of Period (Per) and Cryptochrome (Cry) genes, as well as that of clock-controlled genes (CCGs). In the cytoplasm, PERIOD and CRYPTOCHROME proteins heterodimerize, enter the nucleus and interact with BMAL1/CLOCK, inhibiting the transactivation of their own promoters (negative feedback). BMAL1 and CLOCK also stimulate the transcription of Rev-Erba and Rora (Adapted from Tosini et al., BioEssays, 2008).