title: MYC association with cancer risk and a new model of MYC-mediated repression.
abstract: MYC is one of the most frequently mutated and overexpressed genes in human cancer but the regulation of MYC expression and the ability of MYC protein to repress cellular genes (including itself) have remained mysterious. Recent genome-wide association studies show that many genetic polymorphisms associated with disease risk map to distal regulatory elements that regulate the MYC promoter through large chromatin loops. Cancer risk-associated single-nucleotide polymorphisms (SNPs) contain more potent enhancer activity, promoting higher MYC levels and a greater risk of disease. The MYC promoter is also subject to complex regulatory circuits and limits its own expression by a feedback loop. A model for MYC autoregulation is discussed which involves a signaling pathway between the PTEN (phosphatase and tensin homolog) tumor suppressor and repressive histone modifications laid down by the EZH2 methyltransferase.
authors.affiliation: Departments of Pharmacology and Genetics, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03756.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cole
mesh_terms: D019175:DNA Methylation / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D063185:Epigenetic Repression / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase