Journal article
Differential repression of human and mouse TERT genes during cell differentiation
Nucleic acids research, Vol.37(8), pp.2618-2629
05/2009
Handle:
https://hdl.handle.net/2376/113313
PMCID: PMC2677880
PMID: 19270068
Abstract
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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Details
- Title
- Differential repression of human and mouse TERT genes during cell differentiation
- Creators
- Shuwen Wang - Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine, Hershey, PA 17033, USAYuanjun Zhao - Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine, Hershey, PA 17033, USAChunguang Hu - Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine, Hershey, PA 17033, USAJiyue Zhu - Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Publication Details
- Nucleic acids research, Vol.37(8), pp.2618-2629
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Oxford University Press
- Identifiers
- 99900547598201842
- Language
- English
- Resource Type
- Journal article