Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila.
Aberrant accumulation of the Myc oncoprotein propels proliferation and induces carcinogenesis. In normal cells, however, an abundance of Myc protein represses transcription at the c-myc locus. Cancer cells often lose this autorepression. We examined the control of myc in Drosophila and show here that the Drosophila ortholog, dmyc, also undergoes autorepression. We find that the developmental repressor Polycomb (Pc) is required for dmyc autorepression, and that this Pc-dMyc-mediated repression spreads across an 875-kb region encompassing the dmyc gene. To further investigate the relationship between Myc and Polycomb, we used microarrays to identify genes regulated by each, and identify a striking relationship between the two: A large set of dMyc activation targets is normally repressed by Pc, and 73% of dMyc repression targets require Pc for this repression. Chromatin immunoprecipitation confirmed that many dMyc-Pc-repressed loci have an epigenetic mark recognized by Pc. Our results suggest a novel relationship between Myc and Polycomb, wherein Myc enhances Polycomb repression in order to repress targets, and Myc suppresses Polycomb repression in order to activate targets.
Goodliffe
Julie M
JM
Department of Molecular Biology, Princeton University, New Jersey 08544, USA. jgoodlif@princton.edu
Wieschaus
Eric
E
Cole
Michael D
MD
D000818:Animals; D002843:Chromatin / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1; D040641:Quantitative Trait Loci / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; C066770:Pc protein, Drosophila; D014157:Transcription Factors; D063150:Polycomb Repressive Complex 1