Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis

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.

doi:10.1038/onc.2017.285

Title: Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis

Journal Article · Mon Aug 28 00:00:00 EDT 2017 · Oncogene

DOI:https://doi.org/10.1038/onc.2017.285· OSTI ID:1532258

Park, J-L ^[1]; Lee, Y-S ^[2]; Song, M-J ^[3]; Hong, S-H ^[2]; Ahn, J-H ^[4]; Seo, E-H ^[1]; Shin, S-P ^[5]; Lee, S-J ^[6]; Johnson, B. H. ^[7]; Stampfer, M. R. ^[8]; Kim, H-P ^[9]; Kim, S-Y ^[1]; Lee, Y. S. ^[10]

Korea Research Inst. of Bioscience and Biotechnology (KRIBB), Daejeon (Korea). Personalized Genomic Medicine Research Center; Univ. of Science and Technology, Daejeon (Korea). Dept. of Functional Genomics
National Cancer Center, Goyang-si (Korea). Rare Cancer Branch, Research Inst.
Yonsei Univ. College of Medicine, Seoul (Korea)
Kyung Hee Univ., Seoul (Korea). Dept. of Life and Nanopharmaceutical Sciences and Dept. of Oriental Pharmacy
National Cancer Center, Goyang-si (Korea). Immunotherapeutics Branch, Research Inst.
National Cancer Center, Goyang-si (Korea). Immunotherapeutics Branch, Research Inst.
Univ. of Texas Medical Branch, Galveston, TX (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Yonsei Univ. College of Medicine, Seoul (Korea). Inst. of Tropical Medicine; Yonsei Univ. College of Medicine, Seoul (Korea). Brain Korea 21 Plus Project for Medical Science
Univ. of Texas Medical Branch, Galveston, TX (United States); National Cancer Center, Goyang (Republic of 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. Hypermethylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. Finally, 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Research Foundation of Korea (NRF)

Grant/Contract Number:: AC02-05CH11231; RSG-12-187-01—RMC; RF-2012M3A9D1054670; 2016R1A2B4014183; 2017M3C9A5029978

OSTI ID:: 1532258

Journal Information:: Oncogene, Vol. 36, Issue 49; ISSN 0950-9232

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 18 works

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