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Oncogene. 2017 Dec 7;36(49):6793-6804. doi: 10.1038/onc.2017.285. Epub 2017 Aug 28.

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

Author information

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

Abstract

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.

PMID:
28846112
DOI:
10.1038/onc.2017.285
[Indexed for MEDLINE]

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