Fig. 4: Modeling insights into the mechanism that CHRONO regulates the circadian period.
From: CHRONO regulates the circadian clock via the REV-ERBα – BMAL1 loop
A Diagram of the network of interacting components of the circadian model I incorporating the CHRONO/REV-ERBα loop. B When CHRONO is knocked out in the model, the period of BMAL1 expression is prolonged. C The expression level of REV-ERBα in the situation of CHRONO knockout is increased in the model simulation results. D The expression level of REV-ERBβ in the situation of CHRONO knockout is not affected. E When CHRONO is overexpressed, BMAL1 loses the rhythmicity of its expression. F Overexpression of CHRONO strongly represses the expression of REV-ERBα. The model recapitulates the experimentally observed differential period response due to lack of CHRONO. Solid black lines represent the control WT condition, while dash-dotted lines represent CHRONO−/−. The red lines represent the simulated CHRONO expression in WT (B) and U2OS-CHR cells (E). G The luminescence trace of PC9-CHRONO−/− cell line, which harbors a luciferase reporter driven by the Bmal1 promoter (Bmal1::Luc). H CHRONO knockout in PC9 cell line showed prolonged period, which agreed with model predictions. Data are presented as the mean ± SD.
