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Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis

机译:RNA聚合酶III转录在早期乳腺肿瘤发生中的表观遗传调控

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摘要

RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.
机译:RNA 聚合酶 III (Pol III) 转录中等大小的非编码 RNA(统称为 Pol III 基因)。Pol III基因的新兴多样化作用表明,单个Pol III基因受到转录和表观遗传因子的微妙调控。在这里,我们报告了尚未得到广泛研究的全球 Pol III 表达/甲基化谱和 Pol III 调控的分子机制,使用 nc886 作为代表性的 Pol III 基因。在概括早期乳腺肿瘤发生的人类乳腺上皮细胞系统中,活跃转录的 Pol III 基因的比例增加,在永生化过程中达到平台期。Pol III 基因的高甲基化通过诱导抑制的染色质抑制 Pol III 与 DNA 的结合,并且是 Pol III 库的决定因素。当Pol III基因被低甲基化时,MYC会扩增其转录,而不管其识别DNA基序如何。因此,肿瘤发生过程中的Pol III表达通过甲基化来描述,并通过MYC放大。

著录项

  • 来源
    《Oncogene》 |2017年第49期|6793-6804|共12页
  • 作者单位

    Natl Canc Ctr, Res Inst, Immunotherapeut Branch, Goyang Si, South Korea;

    Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA;

    Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA USAYonsei Univ, Dept Environm Med Biol, Coll Med, Seoul, South KoreaKRIBB, Personalized Genom Med Res Ctr, Daejeon, South KoreaNatl Canc Ctr, Res Inst, Rare Canc Branch, Goyang Si, South KoreaKyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul, South Korea;

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  • 原文格式 PDF
  • 正文语种 英语
  • 中图分类 肿瘤学;
  • 关键词

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