Imperial College London
Alternate

DrWeiCui

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2124wei.cui Website

 
 
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Location

 

1010Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ovando-Roche:2014:10.1002/stem.1725,
author = {Ovando-Roche, P and Yu, JSL and Testori, S and Ho, C and Cui, W},
doi = {10.1002/stem.1725},
journal = {Stem Cells},
pages = {2111--2122},
title = {TRF2-Mediated Stabilization of hREST4 Is Critical for the Differentiation and Maintenance of Neural Progenitors},
url = {http://dx.doi.org/10.1002/stem.1725},
volume = {32},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex that is knownto bind and protect telomeric DNA, yet the detection of TRF2 in extra-telomeric regions of chromosomessuggests other roles for TRF2 besides telomere protection. Here, we demonstrate thatTRF2 plays a critical role in antagonizing the repressive function of neuron-restrictive silencerfactor, also known as repressor element-1 silencing transcription factor (REST), during the neuraldifferentiation of human embryonic stem cells (hESCs) by enhancing the expression of a truncatedREST splice isoform we term human REST4 (hREST4) due to its similarity to rodent REST4.We show that TRF2 is specifically upregulated during hESC neural differentiation concordantlywith an increase in the expression of hREST4 and that both proteins are highly expressed inNPCs. Overexpression of TRF2 in hESCs increases hREST4 levels and induces their neural differentiation,whereas TRF2 knockdown in hESCs and NPCs reduces hREST4 expression, hinderingtheir ability to differentiate to the neural lineage. Concurrently, we show that TRF2 directlyinteracts with the C-terminal of hREST4 through its TRF2 core binding motif [F/Y]xL, protectinghREST4 from ubiquitin-mediated proteasomal degradation and consequently furthering neuralinduction. Thus, the TRF2-mediated counterbalance between hREST4 and REST is vital for boththe generation and maintenance of NPCs, suggesting an important role for TRF2 in both neurogenesisand function of the central nervous system.
AU  - Ovando-Roche,P
AU  - Yu,JSL
AU  - Testori,S
AU  - Ho,C
AU  - Cui,W
DO  - 10.1002/stem.1725
EP  - 2122
PY  - 2014///
SN  - 1549-4918
SP  - 2111
TI  - TRF2-Mediated Stabilization of hREST4 Is Critical for the Differentiation and Maintenance of Neural Progenitors
T2  - Stem Cells
UR  - http://dx.doi.org/10.1002/stem.1725
UR  - http://hdl.handle.net/10044/1/26888
VL  - 32
ER  -
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