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김형표(환경의생물학교실) Oncogene
등록일 : 2017-08-30 오후 12:50:00       조회 : 53
첨   부 :
교신저자 김형표(환경의생물학교실), Kim SY(KRIBB), Lee YS(NCC)
Oncogene. 2017 Aug 28. doi: 10.1038/onc.2017.285. [Epub ahead of print]

Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis.

Park JL1,2, Lee YS3, Song MJ4, Hong SH3, Ahn JH5, Seo EH1,2, Shin SP6, Lee SJ6, Johnson BH7, Stampfer MR8, Kim HP4,9,10, Kim SY1,2, Lee YS7,11.

Author information

1Personalized Genomic Medicine Research Center, KRIBB, Daejeon, Korea.2Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.3Rare Cancer Branch, Research Institute, National Cancer Center, Goyang-si, Korea.4Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul, Korea.5Department of Life and Nanopharmaceutical Sciences and Department of Oriental Pharmacy, Kyung Hee University, Seoul, Korea.6Immunotherapeutics Branch, Research Institute, National Cancer Center, Goyang-si, Korea.7Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, USA.8Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.9Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea.10Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.11Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

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.Oncogene advance online publication, 28 August 2017; doi:10.1038/onc.2017.285.
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