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| Status |
Public on Jul 01, 2007 |
| Title |
TRF2 Inhibition-Mediated Degradation Derepresses the Neuronal Differentiation Program |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Telomere binding factor 2 (TRF2), is a protein that plays a major role in the maintenance of telomere integrity. In mitotic normal and transformed cells, TRF2 inhibition triggers a rapid telomere DNA damage response that results in cell senescence or apoptosis. Here we provide evidence that TRF2 plays a role suppressing neuronal differentiation. TRF2 interacts with the RE1-silencing transcription factor (REST) in nuclear PML protein-containing compartments of neuronal cells in vivo. Inhibition of TRF2 function with a dominant-negative form of TRF2 elicits a telomeric DNA damage response, and disrupts the TRF2-REST complex resulting in proteasomal degradation of REST. Overexpression of REST impairs the ability of DN-TRF2 to induce neuronal differentiation, indicating that enhanced degradation of REST is sufficient to account for the differentiation-inducing effect of DN-TRF2. REST degradation derepresses RE1-regulated genes (L1CAM, BDNF, b3-tubulin, syntaxin and others) resulting in morphological and functional differentiation of neurons. Our findings identify a novel interaction between the telomeric protein TRF2 and REST which regulates the molecular differentiation program of neurons.
Keywords: transfection and molecular inhibition
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| Overall design |
Cells were transfected with GFP vector, WT-TRF2 or DN-TRF2, and were maintained under G418 selection for 7 days. To confirm an inhibitory effect of DN-TRF2 on cell proliferation cells were counted daily during a 4 day post-transfection period. Gene array analysis was performed using NIA MGC1 9600 human gene cDNA microarray on 6 samples; 3 controls and 3 DN-TRF2 positive.
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| Contributor(s) |
Zhang P, Pazin MJ, Becker KG, Dilley CM, Mattson MP |
| Citation(s) |
18818083 |
| |
| Submission date |
Feb 07, 2007 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL1211 |
NIA MGC, Mammalian Genome Collection |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA99295 |
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