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Nucleic Acids Research Advance Access originally published online on March 6, 2009
Nucleic Acids Research 2009 37(8):2618-2629; doi:10.1093/nar/gkp125
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2618-2629
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Differential repression of human and mouse TERT genes during cell differentiation

Shuwen Wang, Yuanjun Zhao, Chunguang Hu and Jiyue Zhu*

Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

*To whom correspondence should be addressed. Tel: +1 (717) 531 3597; Fax: +1 (717) 531 7667; Email: joz1{at}psu.edu

Received January 3, 2009. Revised February 13, 2009. Accepted February 16, 2009.

Differential regulation of telomerase reverse transcriptase (TERT) contributes to the distinct aging and tumorigenic processes in humans and mice. Here, we report that the hTERT gene was strongly repressed during differentiation of human cells, whereas modest mTERT expression was detected in terminally differentiated and post-mitotic cells. The stringent hTERT repression depended on the native chromatin environment because transiently transfected hTERT promoters were not repressed in differentiated cells. Conversely, the transiently transfected mTERT core promoter was repressed during cell differentiation, suggesting that the repression of mTERT promoter did not require its endogenous chromatin structures. To understand the mechanisms of this differential regulation, we examined chromatin structures of the endogenous TERT loci during cell differentiation. In both human and mouse cells, repression was accompanied by the loss of multiple DNase I hypersensitive sites at the TERT promoters and their upstream regions, revealing positions of potential regulatory elements. Interestingly, the hTERT locus was located within a nuclease-resistant chromatin domain in human cells, whereas a corresponding chromatin domain was not detected for the mTERT locus. Taken together, our study indicated that, unlike the repression of mTERT gene, the condensed native chromatin environment of hTERT locus was central to its silencing during cell differentiation.


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S. Wang, Y. Zhao, M. A. Leiby, and J. Zhu
Studying human telomerase gene transcription by a chromatinized reporter generated by recombinase-mediated targeting of a bacterial artificial chromosome
Nucleic Acids Res., September 1, 2009; 37(17): e111 - e111.
[Abstract] [Full Text] [PDF]


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