MYC-associated factor MAX is an essential repressor of the clock core network

The molecular core clock network is based on interconnected feedback loops linking activators and repressors of clock-controlled genes. This study reveals that the MYC-Associated factor X, MAX, plays an essential repressive role in this transcriptional-translational feedback loop. MAX operates through a MYC-independent binding to E-box regions within the promoters of circadian BMAL1 targets. This clock function of MAX is essential for maintaining a proper circadian rhythm but separated by the role of MAX as a partner of MYC in controlling cell proliferation. We also identified MAX Network Transcriptional Repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. In conclusion, our data has demonstrated MAX is an essential part of the core molecular clock and keeps the balance between clock activators and repressors. Accordingly, alteration of MAX transcriptional complexes may contribute to circadian dysfunction in pathological contexts.