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Telomerase modulates Wnt signalling by association with target gene chromatin.
Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, Chang W, Meng Z, Cheung P, Ji H, McLaughlin M, Veenstra TD, Nusse R, McCrea PD, Artandi SE.
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Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-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/beta-catenin signalling by serving as a cofactor in a beta-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/beta-catenin signalling pathway.
Armanios,
Syndromes of telomere shortening.
2009, Pubmed
Armanios,
Syndromes of telomere shortening.
2009,
Pubmed Armstrong,
Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage.
2005,
Pubmed Artandi,
Constitutive telomerase expression promotes mammary carcinomas in aging mice.
2002,
Pubmed Barker,
The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation.
2001,
Pubmed Carrera,
Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13.
2008,
Pubmed Choi,
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
2008,
Pubmed Daniels,
Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation.
2005,
Pubmed Dubrulle,
Coupling segmentation to axis formation.
2004,
Pubmed Erdmann,
Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice.
2004,
Pubmed Farazi,
Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression.
2006,
Pubmed Firestein,
CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.
2008,
Pubmed Flores,
Effects of telomerase and telomere length on epidermal stem cell behavior.
2005,
Pubmed Gat,
De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin.
1998,
Pubmed González-Suárez,
Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes.
2001,
Pubmed Greco,
Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development.
1996,
Pubmed Heasman,
Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
1994,
Pubmed
,
Xenbase Henriksson,
Proteins of the Myc network: essential regulators of cell growth and differentiation.
1996,
Pubmed Houle,
Retinoic acid regulation of Cdx1: an indirect mechanism for retinoids and vertebral specification.
2000,
Pubmed
,
Xenbase Huelsken,
Requirement for beta-catenin in anterior-posterior axis formation in mice.
2000,
Pubmed Ikeya,
Wnt-3a is required for somite specification along the anteroposterior axis of the mouse embryo and for regulation of cdx-1 expression.
2001,
Pubmed Imamura,
A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis.
2008,
Pubmed Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase Kim,
Mediator is a transducer of Wnt/beta-catenin signaling.
2006,
Pubmed
,
Xenbase Korinek,
Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4.
1998,
Pubmed Lee,
TERT promotes cellular and organismal survival independently of telomerase activity.
2008,
Pubmed Lee,
Essential role of mouse telomerase in highly proliferative organs.
1998,
Pubmed Lo Celso,
Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours.
2004,
Pubmed Lohnes,
The Cdx1 homeodomain protein: an integrator of posterior signaling in the mouse.
2003,
Pubmed Lustig,
Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.
2002,
Pubmed Major,
New regulators of Wnt/beta-catenin signaling revealed by integrative molecular screening.
2008,
Pubmed Maser,
Connecting chromosomes, crisis, and cancer.
2002,
Pubmed Masutomi,
The telomerase reverse transcriptase regulates chromatin state and DNA damage responses.
2005,
Pubmed McMahon,
Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis.
1989,
Pubmed
,
Xenbase Millar,
Cell biology: The not-so-odd couple.
2009,
Pubmed
,
Xenbase Polakis,
The many ways of Wnt in cancer.
2007,
Pubmed Pownall,
eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus.
1996,
Pubmed
,
Xenbase Rajaraman,
Telomere uncapping in progenitor cells with critical telomere shortening is coupled to S-phase progression in vivo.
2007,
Pubmed Reya,
Wnt signalling in stem cells and cancer.
2005,
Pubmed Sarin,
Conditional telomerase induction causes proliferation of hair follicle stem cells.
2005,
Pubmed Smith,
Telomerase modulates expression of growth-controlling genes and enhances cell proliferation.
2003,
Pubmed Smogorzewska,
Regulation of telomerase by telomeric proteins.
2004,
Pubmed Stewart,
Telomerase contributes to tumorigenesis by a telomere length-independent mechanism.
2002,
Pubmed Van Mater,
Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice.
2003,
Pubmed Venteicher,
Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly.
2008,
Pubmed Ventura,
Restoration of p53 function leads to tumour regression in vivo.
2007,
Pubmed Willert,
Wnt signaling: is the party in the nucleus?
2006,
Pubmed Wong,
Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation.
2000,
Pubmed Wu,
Understanding the words of chromatin regulation.
2009,
Pubmed Wu,
Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths.
2006,
Pubmed Yang,
A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell cycle dynamics, and in vitro differentiation.
2008,
Pubmed Yoshikawa,
Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse.
1997,
Pubmed
