title: Su(z)2 antagonizes auto-repression of Myc in Drosophila, increasing Myc levels and subsequent trans-activation.
abstract: All tumor cell lines that have been tested are defective for Myc auto-repression, and have high levels of Myc produced from wild type loci and re-arranged loci. Like mammalian Myc auto-repression, Myc protein represses the expression of its gene, dmyc, in Drosophila. This activity requires Polycomb (Pc), since RNAi for Pc in the embryo eliminates Myc auto-repression. We have observed that upon depletion of Polycomb in the embryo, levels of one of 18 different chromatin-binding genetic regulators, Su(z)2, rise dramatically. We pursued the possibility that increased levels of this protein, Su(z)2, interfere with Myc auto-repression, potentially explaining the loss of auto-repression upon Pc RNAi. We report that embryos expressing both ectopic Myc and ectopic Su(z)2 fail in Myc auto-repression. Surprisingly, histone H3K27 tri-methylation at the dmyc locus is inversely correlated with the presence of auto-repression. We show phenotypic consequences of potent dmyc auto-repression, and their complete reversal by ectopic Su(z)2: dmyc auto-repression induced a diminutive (dm) phenotype, and upon elimination of auto-repression by Su(z)2, overall levels of Myc increased and completely rescued the phenotype. We show that this increase in Myc levels caused dramatic activation of Myc activation targets. These data suggest that Su(z)2 is capable of increasing the potency of Myc activity by eliminating Myc's feedback regulation by auto-repression. Although Su(z)2 eliminated Myc auto-repression, we found that Myc repression of other genes is not affected by Su(z)2. These data suggest a unique antagonistic role for Su(z)2 in Myc auto-repression, and a potential mechanism for cancer-cell specific loss of Myc auto-repression.
authors.affiliation: Department of Biology, The University of North Carolina, Charlotte, NC, USA.
authors.forename: Abid
authors.initials: A
authors.lastname: Khan
authors.forename: Wesley
authors.initials: W
authors.lastname: Shover
authors.forename: Julie M
authors.initials: JM
authors.lastname: Goodliffe