Molecular Medicine Research Line, Fondazione Istituto Italiano di Tecnologia (IIT), 16135 Genoa, Italy.
Center for Genomic Science, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.
Int J Mol Sci. 2020 Mar 26;21(7):2294. doi: 10.3390/ijms21072294.
The circadian transcriptional network is based on a competition between transcriptional activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that the MYC-associated factor X, MAX, plays a repressive role in this network and operates through a MYC-independent binding to E-box-containing regulatory regions within the promoters of circadian BMAL1 targets. We further show that this "clock" function of MAX is required for maintaining a proper circadian rhythm and that MAX and BMAL1 contribute to two temporally alternating transcriptional complexes on clock-regulated promoters. We also identified MAX network transcriptional repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. Collectively, our data indicate that MAX regulates clock gene expression and contributes to keeping the balance between positive and negative elements of the molecular clock machinery.
昼夜节律转录网络基于转录激活因子和转录抑制因子复合物之间的竞争，调节时钟控制基因的节律表达。我们在这里表明，MYC 相关因子 X（MAX）在这个网络中发挥抑制作用，并通过 MYC 独立结合到昼夜节律 BMAL1 靶基因启动子中含有 E 盒的调节区域来发挥作用。我们进一步表明，MAX 的这种“时钟”功能对于维持适当的昼夜节律是必需的，并且 MAX 和 BMAL1 有助于在时钟调节启动子上两个时间上交替的转录复合物。我们还鉴定了 MAX 网络转录抑制剂 MNT，作为 MAX 介导的昼夜节律调节的基本伴侣。总的来说，我们的数据表明 MAX 调节时钟基因的表达，并有助于维持分子钟机制中正负元件之间的平衡。
