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J. Biol. Chem., Vol. 275, Issue 46, 35665-35668, November 17, 2000
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From the Department of Pathology and Molecular Medicine, McMaster
University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5,
Canada
Trancriptional regulation of the human telomerase
reverse transcriptase (hTERT) gene, encoding the catalytic
protein of human telomerase, plays a critical role in the activation of
the enzyme during cell immortalization and tumorigenesis. However, the
molecular mechanisms involved in the regulation of hTERT
expression are still not fully understood. We have previously cloned
and characterized the genomic sequences and promoter of the
hTERT gene. Here, we provide evidence that histone
deacetylation is involved in the repression of hTERT in
human cells. Inhibition of histone deacetylases by trichostatin A
in telomerase-negative cells resulted in activation of
telomerase activity and up-regulation of hTERT mRNA.
Transient transfection experiments with a reporter under control of the hTERT promoter indicated that this promoter can be
activated by trichostatin A. Finally, our results show that repression
of the hTERT promoter by the Mad protein requires
histone deacetylase activity, whereas de-repression by trichostatin A
is independent of the E-boxes located in its core region.
ACCELERATED PUBLICATION
Histone Deacetylation Is Involved in the Transcriptional
Repression of hTERT in Normal Human Cells*
*
This work was supported by a grant from the National Cancer
Institute of Canada.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 905-525-9140, ext. 22296; Fax: 905-546-9940; E-mail: bacchett@fhs.mcmaster.ca.
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