TRF2 downregulation acts as an upstream driver of heart failure
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE285948 | GEO | 2026/01/04
REPOSITORIES: GEO
Similar Datasets
Project description:TRF2 downregulation acts as an upstream driver of heart failure
| PRJNA1207027 | ENA
Project description:We report the TRF2 binding sites in post mitotic mammalian cells under TRF2 (protein level) modulation. By obtaining sequences from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of differentiated muscle cells (myotubes). Importantly we find that TRF2 levels are correlated with age (R= 0.60) making our results of importance in regards of the changes that occur in the chromatin landscape upon aging. We found multiple TRF2 binding sites that are conserved across cell types (Young et al., 2008, Simonet et al., 2011) highlighting the central role of TRF2 as a key chromatin modifier and gene regulator.
2017-10-17 | GSE88983 | GEO
Project description: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
2007-07-01 | GSE6983 | GEO
Project description:Telomeres, the nucleoprotein structures located at the end of eukaryotic DNA, protect chromosomal integrity. These structures undergo changes during development and aging, including length shortening and alterations in the levels of the proteins associated to them called shelterin, all this affecting genome stability as the cells age. However, telomeres also behave as transcriptional regulators acting not only on genes present at subtelomeres but also on more distantly located genes presented throughout the genome. This process is referred as Telomere Position Effect (TPE). Here we set to determine whether telomere shortening in senescent cells impact TPE and senescent cells transcriptome. We also investigate whether TRF2 (a shelterin protein) and Lamin B1 (a member of nuclear lamina) are involved in TPE by doing RNA sequencing of young and senescent cells in which we modulated TRF2 and Lamin B1 expression.
2023-03-02 | GSE180406 | GEO
Project description:Taf7l (a paralogue of Taf7) and Trf2 (a TBP-related protein) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility and compromised fertility. Here we find that continued backcrossing of Taf7l-/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-seq analysis of wild type (WT) and Taf7l-/Y (KO) testes revealed that Taf7l ablation impairs the expression of many post-meiotic spermatogenic specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l-/Y mice develop post-meiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2-/- mice, but distinct from Taf4b-/- mice. Indeed, we find that Taf7l and Trf2 co-regulate post-meiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-seq studies indicate that TAF7L binds to promoters of activated post-meiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of post-meiotic genes to regulate spermiogenesis. Our findings thus provide a new mechanism for cell-type specific transcriptional control involving an interaction between a ‘non-prototypic’ core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription. Genome-wide mapping of TAF7L and Pol II in testis tissue, and mRNA-seq expression profiling wild type and Taf7l knockout testis.
2013-09-29 | E-GEOD-50807 | biostudies-arrayexpress
Project description:TRF2 is a paralogue of TATA-box binding protein (TBP) with highest expression in testis. Although Trf2 inactivation in mice leads to arrested spermatogenesis, there is no direct evidence that Trf2 is recruited to chromatin to directly regulate gene expression. We used genetically modified mice where endogenous Trf2 has been modified to carry a TAP-TAG to perform ChIP-reChIP followed by deep sequencing. We found that Trf2 is recruited to all active promoters as a subunit of TFIIA/ALF complex together with TBP. To assess the effect of Trf2 inactivation on gene expression we performed RNA-seq on WT and Trf2-/- testes at 21 days of age when haploid cell gene expression is activated.
2016-08-31 | GSE79602 | GEO
Project description:Here we use ChIP-seq in Drosophila embryos to determine the genome-wide binding pattern of TBP and Trf2 using two different antibodies for each factor. ChIP-seq using anti-Trf2 and anti-TBP antibodies in Drosophila embryos
2014-06-04 | E-GEOD-52029 | biostudies-arrayexpress
Project description:Background: The Telomeric Repeat binding Factor 2 (TRF2), a key protein involved in telomere integrity, is over-expressed in several human cancers and promotes tumor formation and progression. Recently, TRF2 has been also found outside telomeres where it can affect gene expression. Here we provide evidence that TRF2 is able to modulate the expression of microRNAs (miRNAs), small non-coding RNAs altered in human tumors. Among the miRNAs regulated by TRF2, we focused on the miR-193b-3p, an oncomiRNA that positively correlates with TRF2 expression in human colorectal cancer patients. At the mechanistic level, the control of miR-193b-3p expression requires the cooperative activity between TRF2 and the chromatin organization factor CTCF. We found that CTCF physically interacts with TRF2, thus driving the proper positioning of TRF2 on a binding site located upstream the miR-193b-3p host-gene. The binding of TRF2 on the identified region is necessary for promoting the expression of miR-193b3p which, in turn, inhibits the translation of the onco-suppressive methyltransferase SUV39H1 and promotes tumor cell proliferation. The translational relevance of the oncogenic properties of miR-193b-3p was confirmed in patients, in whom the association between TRF2 and miR-193b-3p has a prognostic value.
2022-03-17 | GSE186022 | GEO
Project description:Cellular senescence is accompanied by profound changes in telomere and heterochromatin structure that contribute to ageing. Telomere shortening is a key driver of replicative senescence that activate DNA damage response signaling ending on a p53-dependent downregulation of the shelterin subunit TRF2. Restoring the levels of TRF2 in pre-senescent cells leads to delay entry into senescent and restoration of constitutive heterochromatin structure and damage. Here we set to determine whether the restoration of TRF2 levels change the senescent program by doing RNA-sequencing of senescent cells transduced with a TRF2-expressing lentivirus or an empty lentivirus control.
2022-06-27 | GSE160503 | GEO
Project description:Taf7l (a paralogue of Taf7) and Trf2 (a TBP-related protein) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility and compromised fertility. Here we find that continued backcrossing of Taf7l-/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-seq analysis of wild type (WT) and Taf7l-/Y (KO) testes revealed that Taf7l ablation impairs the expression of many post-meiotic spermatogenic specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l-/Y mice develop post-meiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2-/- mice, but distinct from Taf4b-/- mice. Indeed, we find that Taf7l and Trf2 co-regulate post-meiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-seq studies indicate that TAF7L binds to promoters of activated post-meiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of post-meiotic genes to regulate spermiogenesis. Our findings thus provide a new mechanism for cell-type specific transcriptional control involving an interaction between a ‘non-prototypic’ core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription.
2013-09-29 | GSE50807 | GEO