Published online 2 December 2005
Article |
CTCF binds the proximal exonic region of hTERT and inhibits its transcription
Institute of Pathology, Centre Hospitalier Universitaire Vaudois Bugnon 25, 1011 Lausanne, Switzerland 1Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Rockville, MD 20892, USA
*To whom correspondence should be addressed. Tel: +41 21 314 7153; Fax: +41 21 314 7115; Email: Jean.Benhattar{at}chuv.hospvd.ch
Received March 24, 2005. Revised June 16, 2005. Accepted November 14, 2005.
The expression of the catalytic subunit (hTERT) represents the limiting factor for telomerase activity. Previously, we detected a transcriptional repressor effect of the proximal exonic region (first two exons) of the hTERT gene. To better understand the mechanism involved and to identify a potential repressor, we further characterized this region. The addition of the hTERT proximal exonic region downstream of the hTERT minimal promoter strongly reduced promoter transcriptional activity in all cells tested (tumor, normal and immortalized). This exonic region also significantly inhibited the transcriptional activity of the CMV and CDKN2A promoters, regardless of the cell type. Therefore, the repressor effect of hTERT exonic region is neither cell nor promoter-dependent. However, the distance between the promoter and the exonic region can modulate this repressor effect, suggesting that nucleosome positioning plays a role in transcriptional repression. We showed by electrophoretic mobility shift assay that CCCTC-binding factor (CTCF) binds to the proximal exonic region of hTERT. Chromatin immunoprecipitaion assays confirmed the binding of CTCF to this region. CTCF is bound to hTERT in cells in which hTERT is not expressed, but not in telomerase-positive ones. Moreover, the transcriptional downregulation of CTCF by RNA interference derepressed hTERT gene expression in normal telomerase-negative cells. Our results suggest that CTCF participates in key cellular mechanisms underlying immortality by regulating hTERT gene expression.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. A. Katzenellenbogen, P. Vliet-Gregg, M. Xu, and D. A. Galloway NFX1-123 Increases hTERT Expression and Telomerase Activity Posttranscriptionally in Human Papillomavirus Type 16 E6 Keratinocytes J. Virol., July 1, 2009; 83(13): 6446 - 6456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chatagnon, S. Bougel, L. Perriaud, J. Lachuer, J. Benhattar, and R. Dante Specific association between the methyl-CpG-binding domain protein 2 and the hypermethylated region of the human telomerase reverse transcriptase promoter in cancer cells Carcinogenesis, January 1, 2009; 30(1): 28 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Svenson, K. Nordfjall, B. Stegmayr, J. Manjer, P. Nilsson, B. Tavelin, R. Henriksson, P. Lenner, and G. Roos Breast Cancer Survival Is Associated with Telomere Length in Peripheral Blood Cells Cancer Res., May 15, 2008; 68(10): 3618 - 3623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A P Moulin, G Clement, F T Bosman, L Zografos, and J Benhattar Methylation of CpG island promoters in uveal melanoma Br J Ophthalmol, February 1, 2008; 92(2): 281 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Renaud, E. M. Pugacheva, M. D. Delgado, R. Braunschweig, Z. Abdullaev, D. Loukinov, J. Benhattar, and V. Lobanenkov Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors Nucleic Acids Res., December 18, 2007; 35(21): 7372 - 7388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chernukhin, S. Shamsuddin, S. Y. Kang, R. Bergstrom, Y.-W. Kwon, W. Yu, J. Whitehead, R. Mukhopadhyay, F. Docquier, D. Farrar, et al. CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide Mol. Cell. Biol., March 1, 2007; 27(5): 1631 - 1648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Renaud, D. Loukinov, Z. Abdullaev, I. Guilleret, F. T. Bosman, V. Lobanenkov, and J. Benhattar Dual role of DNA methylation inside and outside of CTCF-binding regions in the transcriptional regulation of the telomerase hTERT gene Nucleic Acids Res., February 28, 2007; 35(4): 1245 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ghochikyan, M. Mkrtichyan, D. Loukinov, G. Mamikonyan, S. D. Pack, N. Movsesyan, T. E. Ichim, D. H. Cribbs, V. V. Lobanenkov, and M. G. Agadjanyan Elicitation of T Cell Responses to Histologically Unrelated Tumors by Immunization with the Novel Cancer-Testis Antigen, Brother of the Regulator of Imprinted Sites J. Immunol., January 1, 2007; 178(1): 566 - 573. [Abstract] [Full Text] [PDF]
|
|