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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: Neurol Clin. 2019 May 29;37(3):487–504. doi: 10.1016/j.ncl.2019.05.002

Figure 1. Multidimensional genetic clockwork.

Figure 1

The core clock of animals has the proteins CLOCK and BMAL1 functioning as positive regulators, binding to E-box regulatory elements and transactivating the transcription of the per and Cry genes, as well as multiple other rhythmically expressed genes. Phosphorylation of PER by CSNK1 can lead to its degradation. PER and CRY proteins form dimers and enter the nucleus to repress the CLOCK:BMAL1 complex. Rhythmic transcription leads to rhythms in key regulator genes and cellular functions that can feedback to alter core clock function. In addition, CLOCK affects histone acetylation, another mechanism by which gene activity can be modulated.