Module 4: Figure Myc as a gene repressor
Myc represses genes activated by Miz1.
Activation of some of the cyclin-dependent kinase (CDK) inhibitors, such as p15 and p21, are repressed by Myc. A. The p21 gene, which is activated through UV irradiation and p53, is also activated at the initiator (INR) site by Miz1, which binds p300 that acts to acetylate chromatin to open up the locus for transcription. Myc/Max dimers inhibit this transcription by binding to Miz1 to displace the p300, and it also brings in the DNA methyltransferase DNMT3a. B. The p15 gene is also activated by Miz1. This gene is also controlled by transforming growth factor β (TGF-β), which has two actions. It uses activated Smad1/4 to bind to the serum response element (SRE) site, and it also inhibits Myc, which is a potent repressor of Miz1. An increase in Myc levels can silence this gene.