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dc.contributor.authorAnderson, CJ
dc.contributor.authorHoare, SF
dc.contributor.authorAshcroft, M
dc.contributor.authorBilsland, AE
dc.contributor.authorKeith, WN
dc.identifier.citationONCOGENE, 2006, 25 pp. 61 - 69
dc.description.abstractBasal telomerase activity is dependent on expression of the hTERT and hTR genes and upregulation of telomerase gene expression is associated with tumour development. It is therefore possible that signal transduction pathways involved in tumour development and features of the tumour environment itself may influence telomerase gene regulation. The majority of solid tumours contain regions of hypoxia and it has recently been demonstrated that hypoxia can increase telomerase activity by mechanisms that are still poorly defined. Here, we show that hypoxia induces the transcriptional activity of both hTR and hTERT gene promoters. While endogenous hTR expression is regulated at the transcriptional level, hTERT is subject to regulation by alternative splicing under hypoxic conditions, which involves a switch in the splice pattern in favour of the active variant. Furthermore, analysis of the chromatin landscape of the telomerase promoters reveals dynamic recruitment of a transcriptional complex involving the hypoxia- inducible factor-1 transcription factor, p300, RNA polymerase II and TFIIB, to both promoters during hypoxia, which traffics along and remains associated with the hTERT gene as transcription proceeds. These studies show that hTERT and hTR are subject to similar controls under hypoxia and highlight the rapid and dynamic regulation of the telomerase genes in vivo.
dc.format.extent61 - 69
dc.titleHypoxic regulation of telomerase gene expression by transcriptional and post-transcriptional mechanisms
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
pubs.notesaffiliation: Keith, WN (Reprint Author), Univ Glasgow, Canc Res UK, Beatson Labs, Ctr Oncol & Appl Pharmacol, Alexander Stone Bldg,Garscube Estate,Switchback R, Glasgow G61 1BD, Lanark, Scotland. Univ Glasgow, Canc Res UK, Beatson Labs, Ctr Oncol & Appl Pharmacol, Glasgow G61 1BD, Lanark, Scotland. Inst Canc Res, Canc Res UK, Ctr Canc Therapeut, Sutton, Surrey, England. keywords: telomerase; hTR; hTERT; hypoxia; RNA splicing; chromatin keywords-plus: STRESS-INDUCED APOPTOSIS; HUMAN CANCER-CELLS; INDUCIBLE FACTOR-1-ALPHA; BACTERIAL NITROREDUCTASE; REVERSE-TRANSCRIPTASE; TUMOR-GROWTH; LIFE-SPAN; IN-VIVO; ACTIVATION; HTERT research-areas: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity web-of-science-categories: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity author-email: [email protected] researcherid-numbers: Keith, Nicol/D-3325-2009 Bilsland, Alan/G-2629-2010 Cairney, Claire/H-6989-2012 orcid-numbers: Keith, Nicol/0000-0001-7862-3580 Cairney, Claire/0000-0001-6531-245X Bilsland, Alan/0000-0003-0957-3908 number-of-cited-references: 34 times-cited: 62 usage-count-last-180-days: 0 usage-count-since-2013: 4 journal-iso: Oncogene doc-delivery-number: 999QX unique-id: ISI:000234406400007 oa: gold_or_bronze da: 2018-09-04
pubs.notesNot known
pubs.embargo.termsNot known
dc.contributor.icrauthorAshcroft, Margareten

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