Gene expression data after acute withdrawal of TERT in mouse skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE9725 | GEO | 2007/12/13
SECONDARY ACCESSION(S): PRJNA103639
REPOSITORIES: GEO
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Project description:TERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT. We performed time-course microarray analysis using conditional bi-transgenic mice (iK5-TERT) to understand the mechanism of this novel non-telomeric function of TERT. Experiment Overall Design: Hair follicles of iK5-TERT mice at postnatal day 60 is in TERT-induced anagen. To those mice, we injected either PBS, to maintain TERT transgene expression, or doxycycline, to rapidly extinguish transgene expression. We then took time-course dorsal skin biopsies (0,6,12,24 hr) of these mice and analyzed differential gene expressions using Affymetrix Genechips and various bioinformatic tools, including SAM, to discover TERT-regulated genes.
2008-06-17 | E-GEOD-9725 | biostudies-arrayexpress
Project description:Telomeres are the nucleoprotein structures found at the ends of eukaryotic chromosomes. Conventional DNA polymerases are unable to fully replicate the telomeric end of the chromosome, which leads to a progressive loss of DNA after every cell division. This problem is solved by the ribonucleoprotein enzyme, telomerase. Proper maintenance of the telomeric end is critical for maintaining genome integrity in eukaryotes. The telomerase enzyme has two essential components: the telomerase RNA (TR), which provides the template required for telomeric DNA synthesis; and the catalytic protein telomerase reverse transcriptase (TERT) that catalyzes the extension of the telomeric DNA ends using the TR as a template. The action of telomerase prevents the progressive shortening of the telomeres after every cell division. The TR can form a large structural scaffold upon which many accessory proteins can bind to and form the complete telomerase holoenzyme in vivo. These accessory proteins are required for telomerase activity and regulation inside of cells. The interacting partners of the TERT protein have been extensively characterized in yeast, human, and Tetrahymena systems. These interactors have not been extensively studied in lower eukaryotes including clinically relevant human parasites, such as Trypanosoma brucei (T. brucei). To this end, we performed co-immunoprecipitation coupled to LC-MS/MS of TbTERT-FLAG-HA-HA from T. brucei cells using an anti-TbTERT antibody and protein G magnetic beads. An isotype matched IgG control was performed in tandem. Comparisons of enriched proteins in the IP vs. IgG control revealed previously known and novel interactors of TbTERT. These findings suggest potential mechanistic differences in telomere maintenance in T. brucei compared to higher eukaryotes.
2023-03-08 | PXD038235 | Pride
Project description:Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observed that expression of telomerase reverse transcriptase (TERT) is closely associated with immune-suppressive signatures. We demonstrated that TERT can activate a subclass of endogenous retroviruses (ERVs) to form double-stranded RNAs (dsRNAs), which were sensed by the RIG-1/MDA5-MAVS signalling pathway and triggered interferon signalling in cancer cells. Furthermore, we showed that TERT-induced ERVs/interferon signalling stimulated the expression of chemokines, including CXCL10, which induced suppressed T cell infiltration with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERVs/interferon signalling contributes to immune suppression in tumours.
2022-02-22 | GSE169714 | GEO
Project description:Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observed that expression of telomerase reverse transcriptase (TERT) is closely associated with immune-suppressive signatures. We demonstrated that TERT can activate a subclass of endogenous retroviruses (ERVs) to form double-stranded RNAs (dsRNAs), which were sensed by the RIG-1/MDA5-MAVS signalling pathway and triggered interferon signalling in cancer cells. Furthermore, we showed that TERT-induced ERVs/interferon signalling stimulated the expression of chemokines, including CXCL10, which induced suppressed T cell infiltration with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERVs/interferon signalling contributes to immune suppression in tumours.
2022-02-22 | GSE169713 | GEO
Project description:Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observed that expression of telomerase reverse transcriptase (TERT) is closely associated with immune-suppressive signatures. We demonstrated that TERT can activate a subclass of endogenous retroviruses (ERVs) to form double-stranded RNAs (dsRNAs), which were sensed by the RIG-1/MDA5-MAVS signalling pathway and triggered interferon signalling in cancer cells. Furthermore, we showed that TERT-induced ERVs/interferon signalling stimulated the expression of chemokines, including CXCL10, which induced suppressed T cell infiltration with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERVs/interferon signalling contributes to immune suppression in tumours.
2022-02-22 | GSE169711 | GEO
Project description:Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity. We transferred intact human chromosome 5 into mouse melanoma B16F10 cells by microcell fusion. The microcell hybrids (MH5) exhibited suppression of telomerase, we also obtained revertant clones (MH5R) in which telomerase is reactivated. To identify the differentially expressed genes on human chromosome 5, we performed expression microarray analysis using these two clones and parental B16F10 cells.
2010-09-10 | E-GEOD-23216 | biostudies-arrayexpress
Project description:A recent study by Castelo-Branco, P., et al. Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 2013;14:534-542 found upstream of the transcription start site (UTSS) hypermethylation of TERT is associated with tumor progression and poor prognosis in paediatric brain tumours. They interpreted that the UTSS region of telomerase reverse transcriptase (TERT) gene is a potentially accessible biomarker for various cancers. This study, we aimed to explore the role of TERT in hepatocellular carcinoma (HCC) and to investigate whether the UTSS region of TERT promoter shows the same methylation pattern in HCC.
2015-01-03 | GSE63863 | GEO
Project description:Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity.
2010-09-10 | GSE23216 | GEO
Project description:Blocking telomerase is recognized as a key anti-cancer mechanism. Unlike in stem cells, levels of telomerase catalytic subunit TERT are limiting in reconstituting telomerase activity in somatic cells. However in some cancers, Tert is transcriptionally reactivated by mutations in its promoter. Given that Tert in stem cells is driven by WT Tert promoter, if we can selectively target Tert reactivation through mutant Tert promoters we can block telomerase activity specifically in cancer cells without toxicity in stem cells. Here we report the epigenetic regulation of Tert promoter comparing WT and mutant promoters. We showed that GABPA homodimerization through long-range interaction stabilizes Gabpa to drive Tert expression. Furthermore, BRD4 specifically activates the C250T mutant promoter via dual mechanism involving GABPA, thereby setting the stage for future therapeutics.
2017-02-27 | GSE77265 | GEO
Project description:A recent study by Castelo-Branco, P., et al. Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 2013;14:534-542 found upstream of the transcription start site (UTSS) hypermethylation of TERT is associated with tumor progression and poor prognosis in paediatric brain tumours. They interpreted that the UTSS region of telomerase reverse transcriptase (TERT) gene is a potentially accessible biomarker for various cancers. This study, we aimed to explore the role of TERT in hepatocellular carcinoma (HCC) and to investigate whether the UTSS region of TERT promoter shows the same methylation pattern in HCC. We analyzed a methylation assay of TERT including the UTSS region in 125 paired HCC samples using Mass Array EpiTyper (Sequenom, SanDiego, CA, USA). To obtain the relationship between TERT promoter methylation status and TERT expression level, we analysed a validation group of 12 paired HCC samples and acquired the FPKM value of TERT gene.
2015-01-03 | E-GEOD-63863 | biostudies-arrayexpress