Biology

Transcriptional repression by the proximal exonic region at the human TERT gene

Document Type

Article

Abstract

In humans, the enzyme telomerase (hTERT) is responsible for the synthesis of new repeat sequences at the telomeres of chromosomes. Although active in early embryogenesis, the hTERT gene is transcriptionally silenced in almost all somatic cells in the adult, but is aberrantly re-activated in over 90% of human cancers. The molecular mechanisms responsible for repression of this gene are thought to involve the transcription factor CTCF. In this study, we bioinformatically identify putative CTCF binding sites in the hTERT proximal exonic region (PER) and determine their functional relevance in mediating transcriptional silencing at this gene. Tests using a reporter gene assay in HeLa cancer cells demonstrate that a sub-region of the PER exhibits strong transcriptional repressive activity. This repression is independent of the previously identified CTCF binding site near the transcriptional start site of the hTERT gene. In addition, site directed mutagenesis of three predicted CTCF binding sites, including a previously characterized in vivo site in exon 2, does not result in a loss of the repression mediated by the PER. The results from this study indicate that expression of the hTERT gene in HeLa cells is regulated by sequences in the PER. This transcriptional control is mediated through additional regulatory molecular mechanisms, independent of CTCF binding. © 2011 Elsevier B.V.

Publication Title

Gene

Publication Date

10-15-2011

Volume

486

Issue

1-2

First Page

65

Last Page

73

ISSN

0378-1119

DOI

10.1016/j.gene.2011.07.016

Keywords

cis-regulation, CTCF, repressor, telomerase, TERT, transcription

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