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Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis

Authors
 Park JL  ;  Lee YS  ;  Song MJ  ;  Hong SH  ;  Ahn JH  ;  Seo EH  ;  Shin SP  ;  Lee SJ  ;  Johnson BH  ;  Stampfer MR  ;  Kim HP  ;  Kim SY  ;  Lee YS 
Citation
 ONCOGENE, Vol.36(49) : 6793-6804, 2017 
Journal Title
ONCOGENE
ISSN
 0950-9232 
Issue Date
2017
MeSH
Breast/cytology ; Breast/metabolism ; Cell Transformation, Neoplastic/genetics ; Cells, Cultured ; Chromatin/genetics ; Chromatin/metabolism ; DNA/genetics ; DNA/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Epithelial Cells/metabolism ; Humans ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics ; RNA Polymerase III/metabolism ; RNA, Untranslated/genetics ; Transcription, Genetic
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.
Full Text
http://www.nature.com/articles/onc2017285
DOI
10.1038/onc.2017.285
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
Song, Min Ji(송민지)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161480
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