Telomerase modulates Wnt signalling by association with target gene chromatin
By Jae-Il Park, Andrew S. Venteicher, J. Hong, Jinkuk Choi, Sohee Jun, Marina Shkreli, Woody Chang, Z. Meng, Peggie Cheung, Hong Ji and 5 more. Nature, 2009
721 citations recorded by the source corpus.
Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/β-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/β-catenin signalling by serving as a cofactor in a β-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior–posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert-/- mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/β-catenin signalling pathway.
Subfields: Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/f35c9e02beb9a07609f098c9b197dd785e1a0b54
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In Molecular Biology
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Citations in the corpus
- Genomic maps of lincRNA occupancy reveal principles of RNA-chromatin interactions (2011, background): “It is known that TERT can bind to and coactivate Wnt target genes at chromatin (Park et al., 2009), and we hypothesized that TERC, as a component of the TERT complex, may also co-occupy some of the same genes.”
- Hallmarks of cancer: the next generation. (2011, positive): “Among the growing list of telomere-independent functions of TERT/telomerase is the ability of TERT to amplify signaling by the Wnt pathway, by serving as a cofactor of the b -catenin/LEF transcription factor complex (Park et al., 2009).”