Figure 6: MYC inversely correlates with BMAL1 expression in human lymphomas.

(a) Scatter plots of expression levels of MYC versus the indicated clock genes in 102 human lymphoma samples of the ICGC MMML-Seq project³⁷ (RPKM: log2 sequence reads per kilobase transcript per million reads³⁸). Expression of MYC versus its established target NUCLEOLIN (NCL) is shown as a positive control. (b) Data were binned according to the indicated MYC expression levels. Clock gene expression levels are shown by Box-plots. Significant differences (P<0.05; Student’s t-test) of expression levels relative to box 1 (0–50) and box 2 (50–100) are indicated by asterisks (*) and number signs (#), respectively. (c) Model of the coordinating function of MYC. Left panel: high levels of MYC suppress the circadian clock by MIZ1-dependent downregulation of BMAL1/CLOCK (see text), which results in low amplitude expression rhythms of clock-controlled genes. On the other hand, high MYC levels support cell growth and proliferation (for example, by inhibition of p15 and p21, see text). Right panel: at low levels of MYC, the circadian clock is not inhibited and supports high amplitude expression rhythms of clock-controlled genes. Low levels of MYC do not support cell growth and proliferation.