MYC Association with Cancer Risk and a New Model of MYC-Mediated Repression
MYC Association with Cancer Risk and a New Model of MYC-Mediated Repression
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DOI：
10.1101/cshperspect.a014316
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发表时间：
2014-07-01
影响因子：
5.4
通讯作者：
Cole, Michael D.
中科院分区：
文献类型：
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作者：
Cole, Michael D.
MYC是人类癌症中最常突变和过表达的基因之一，但MYC表达的调节和MYC蛋白抑制细胞基因（包括其自身）的能力仍然是个谜。最近的全基因组关联研究表明，许多与疾病风险相关的遗传多态性映射到通过大染色质环调控MYC启动子的远端调控元件。癌症风险相关的单核苷酸多态性（SNP）含有更有效的增强子活性，促进更高的MYC水平和更大的疾病风险。MYC启动子也受到复杂的调控回路的影响，并通过反馈回路限制其自身的表达。MYC自动调节的模型进行了讨论，其中涉及的PTEN（磷酸酶和张力蛋白同源物）肿瘤抑制剂和抑制性组蛋白修饰的EZH2甲基转移酶奠定之间的信号通路。
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.