Research
Localization of an hTERT repressor region on human chromosome 3p21.3 using chromosome engineering
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* Corresponding author: Hiroyuki Kugoh kugoh@med.tottori-u.ac.jp
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
Genome Integrity 2010, 1:6 doi:10.1186/2041-9414-1-6
Published: 26 May 2010Abstract
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.