Cloning and characterization of human and mouse telomerase RNA gene promoter sequences

Zhao, J.Q., Hoare, S.F., McFarlane, R., Muir, S., Parkinson, E.K., Black, D.M. and Keith, W.N. (1998) Cloning and characterization of human and mouse telomerase RNA gene promoter sequences. Oncogene, 16(10), pp. 1345-1350.

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Publisher's URL: http://www.nature.com/onc/journal/v16/n10/index.html

Abstract

Variation in telomerase activity is correlated with cellular senescence and tumour progression. However, although the enzymatic activity of telomerase has been well studied, very little is known about how expression of telomerase genes is regulated in mammalian cells. We have therefore cloned the promoter regions of the human (hTR), and mouse, (terc), telomerase RNA genes in order to identify the regulatory elements controlling telomerase RNA gene transcription, 1.76 kb encompassing the hTR gene promoter region was sequenced, as was 4 kb encompassing the terc promoter. No significant sequence similarity could be detected in comparisons between human and mouse 5'-regions, flanking the transcribed sequences. However, both the human and mouse telomerase RNA genes are within CpG islands and may therefore be under the regulation of DNA methylation. Transient expression of hTR-reporter gene constructs in HeLa and GM847 cells identified the elements responsible for promoter activity are contained in a 231 bp region upstream of the transcriptional start site, Transient expression of terc-reporter gene constructs in Swiss3T3 and A9 cells identified the elements responsible for promoter activity are contained in a 73 bp region upstream of the transcriptional start site. These studies have implications for novel transcription targeted cancer therapies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hoare, Miss Stacey and Keith, Professor Nicol and McFarlane, Mr Robert and Muir, Dr Scott
Authors: Zhao, J.Q., Hoare, S.F., McFarlane, R., Muir, S., Parkinson, E.K., Black, D.M., and Keith, W.N.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Oncogene
ISSN:0950-9232

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