Telomerase promoter reprogramming and interaction with general transcription factors in the human mesenchymal stem cell

Nedime Serakinci, Stacey F. Hoare, Moustapha Kassem, Stuart P. Atkinson, W. Nicol Keith

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The human adult mesenchymal stem cell (hMSC) does not express telomerase and has been shown to be the target for neoplastic transformation after transduction with hTERT. These findings lend support to the stem cell hypothesis of cancer development but by supplying hTERT, the molecular events required to upregulate hTERT expression in cancer development are missed. Therefore, the hMSC is ideal for the identification of molecular mechanisms regulating telomerase gene expression in stem cells. This study shows that the repression of hTERT expression in hMSC is chromatin based and that modifications of the chromatin environment lead to reactivation of telomerase gene expression. It is shown that repression of hTERT expression in hMSCs is due to promoter-specific histone hypoacetylation coupled with low Pol II and TFIIB trafficking. This repression is overcome by treatment with Trichostatin A (TSA), an HDAC inhibitor, concomitant with increases in promoter-specific histone acetylation and increases in Pol II and TFIIB tracking. hTR expression is also increased in TSA-treated hMSCs, concomitant with changes in Pol II and TFIIB dynamics.
Original languageEnglish
JournalRegenerative Medicine
Volume1
Issue number1
Pages (from-to)125-131
Number of pages6
ISSN1746-0751
DOIs
Publication statusPublished - 1. Jan 2006

Keywords

  • Acetylation
  • Cells, Cultured
  • Chromatin Assembly and Disassembly
  • DNA Polymerase II
  • Gene Expression Regulation
  • Histone Acetyltransferases
  • Humans
  • Mesenchymal Stem Cells
  • Models, Biological
  • Promoter Regions (Genetics)
  • RNA, Untranslated
  • Telomerase
  • Transcription Factor TFIIB
  • Transcription Factors

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