Localization of an hTERT repressor region on human chromosome 3p21.3 using chromosome engineering.
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.
Abe
Satoshi
S
Department of Biomedical Science, Graduate School of Medical Science, and Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago 683-8503, Japan. kugoh@med.tottori-u.ac.jp.
Tanaka
Hiromi
H
Notsu
Tomomi
T
Horike
Shin-Ichi
S
Fujisaki
Chikako
C
Qi
Dong-Lai
DL
Ohhira
Takahito
T
Gilley
David
D
Oshimura
Mitsuo
M
Kugoh
Hiroyuki
H