Research

Localization of an hTERT repressor region on human chromosome 3p21.3 using chromosome engineering

Satoshi Abe^1,2 , Hiromi Tanaka² , Tomomi Notsu³ , Shin-ichi Horike⁴ , Chikako Fujisaki¹ , Dong-Lai Qi¹ , Takahito Ohhira¹ , David Gilley² , Mitsuo Oshimura¹ and Hiroyuki Kugoh¹

¹  Department of Biomedical Science, Graduate School of Medical Science, and Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago 683-8503, Japan

²  Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street, IB-130, Indianapolis, IN 46202-5251, USA

³  Division of Regenerative Medicine and Therapeutics, Graduate School of Medical Science, Tottori University, 86 Nishicho, Yonago 683-8503, Japan

⁴  Frontier Science Organization, Institute for Gene Research, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-0934, Japan

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Genome Integrity 2010, 1:6doi:10.1186/2041-9414-1-6

Published:	26 May 2010

Abstract

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA. The reactivation of telomerase activity by aberrant upregulation/expression of its catalytic subunit hTERT is a major pathway in human tumorigenesis. However, regulatory mechanisms that control hTERT expression are largely unknown. Previously, we and others have demonstrated that the introduction of human chromosome 3, via microcell-mediated chromosome transfer (MMCT), repressed transcription of the hTERT gene. These results suggested that human chromosome 3 contains a regulatory factor(s) involved in the repression of hTERT. To further localize this putative hTERT repressor(s), we have developed a unique experimental approach by introducing various truncated chromosome 3 regions produced by a novel chromosomal engineering technology into the renal cell carcinoma cell line (RCC23 cells). These cells autonomously express ectopic hTERT (exohTERT) promoted by a retroviral LTR promoter in order to permit cellular division after repression of endogenous hTERT. We found a telomerase repressor region located within a 7-Mb interval on chromosome 3p21.3. These results provide important information regarding hTERT regulation and a unique method to identify hTERT repressor elements.