Park J-L, Lee Y-S, Song M-J, Hong S-H, Ahn J-H, Seo E-H, Shin S-P, Lee S-J, Johnson B H, Stampfer M R, Kim H-P, Kim S-Y, Lee Y S
Personalized Genomic Medicine Research Center, KRIBB, Daejeon, Korea.
Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
Oncogene. 2017 Dec 7;36(49):6793-6804. doi: 10.1038/onc.2017.285. Epub 2017 Aug 28.
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.
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基因不断涌现的多种作用表明，单个Pol III基因受到转录和表观遗传因子的精确调控。在此，我们以nc886作为代表性的Pol III基因，报告尚未得到广泛研究的全局Pol III表达/甲基化谱以及Pol III调控的分子机制。在一个概括早期乳腺肿瘤发生的人乳腺上皮细胞系统中，活跃转录的Pol III基因比例在永生化过程中增加并达到平台期。Pol III基因的高甲基化通过诱导染色质抑制来抑制Pol III与DNA的结合，并且是Pol III基因库的一个决定因素。当Pol III基因发生低甲基化时，MYC会放大它们的转录，而不管其识别的DNA基序如何。因此，肿瘤发生过程中的Pol III表达由甲基化来描绘，并由MYC放大。
