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

Journal Article · · Oncogene
 [1];  [2];  [3];  [2];  [4];  [1];  [5];  [6];  [7];  [8];  [9];  [1];  [10]
  1. 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
  2. National Cancer Center, Goyang-si (Korea). Rare Cancer Branch, Research Inst.
  3. Yonsei Univ. College of Medicine, Seoul (Korea)
  4. Kyung Hee Univ., Seoul (Korea). Dept. of Life and Nanopharmaceutical Sciences and Dept. of Oriental Pharmacy
  5. National Cancer Center, Goyang-si (Korea). Immunotherapeutics Branch, Research Inst.
  6. National Cancer Center, Goyang-si (Korea). Immunotherapeutics Branch, Research Inst.
  7. Univ. of Texas Medical Branch, Galveston, TX (United States)
  8. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  9. 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
  10. 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.

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
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

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Cited By (9)

Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy journal February 2020
Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound journal April 2019
Protein kinase R and its cellular regulators in cancer: An active player or a surveillant? journal June 2019
Effects on prostate cancer cells of targeting RNA polymerase III journal March 2019
Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas journal March 2019
nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer journal March 2018
Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy journal February 2020
The multi-faceted regulation of nuclear tRNA gene transcription: Transfer RNA gene expression journal June 2019
Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound journal April 2019

Figures / Tables (6)