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

Satoshi Abe, Hiromi Tanaka, Tomomi Notsu, Shin Ichi Horike, Chikako Fujisaki, Dong Lai Qi, Takahito Ohhira, David Gilley, Mitsuo Oshimura, Hiroyuki Kugoh

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11 Scopus citations

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.

Original languageEnglish (US)
Article number6
JournalGenome Integrity
Volume1
DOIs
StatePublished - May 26 2010

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Abe, S., Tanaka, H., Notsu, T., Horike, S. I., Fujisaki, C., Qi, D. L., Ohhira, T., Gilley, D., Oshimura, M., & Kugoh, H. (2010). Localization of an hTERT repressor region on human chromosome 3p21.3 using chromosome engineering. Genome Integrity, 1, [6]. https://doi.org/10.1186/2041-9414-1-6