Fig. 5: Model for balancing dopamine levels by clock components.
From: Beyond vision: effects of light on the circadian clock and mood-related behaviours
The left part of the model shows the transcriptional regulation of tyrosine hydroxylase gene (Th), encoding the rate-limiting enzyme of dopamine synthesis. Th is regulated by the nuclear receptors ROR, REV-ERB, and NURR1 via the regulatory promoter elements RRE and NR. The right part of the model depicts the regulation of the monoamine oxidase A gene (MaoA), encoding the rate-limiting enzyme of dopamine degradation. MaoA is regulated by BMAL1 (B), CLOCK (C)/NPAS2 (N) via an E-box element present in the MaoA promoter. PER2 can influence both arms of dopamine regulatory genes via interaction with REV-ERB/NURR1 and interference with BMAL1/NPAS2. The hatched lines illustrate a regulatory pathway for REV-ERB present in the liver, involving heat-shock protein 90 (HSP90) and glucocorticoid receptor (GR). This pathway may potentially also be present in the brain.
