TRF2-ChipSeq in post mitotic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE88983 | GEO | 2017/10/17
SECONDARY ACCESSION(S): PRJNA349457
REPOSITORIES: GEO
Similar Datasets
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: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: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: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: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: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.
2016-08-31 | GSE79601 | 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
Project description:Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in termination of the cell cycle checkpoint by counteracting activity of the tumour suppressor protein p53. By dephosphorylating various proteins at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified interaction between PPM1D and the components of the shelterin complex that protects telomeric DNA. Interaction between PPM1D and TRF2 was confirmed by immunoprecipitation and proximity ligation assay. Confocal microscopy revealed colocalisation of the endogenous PPM1D with TRF2 at telomeres. Further, we found that TRF2 was phosphorylated by ATR at S410 after induction of DNA damage at telomeres and this modification was increased in cells lacking PPM1D or after PPM1D inhibition. Phosphorylation of TRF2 stimulated its interaction with TIN2 at telomeres and in vitro. Conversely, overexpression of PPM1D impaired localisation of TIN2 at telomeres. Finally, inhibition of PPM1D impaired recruitment of 53BP1 and RAD51 to DNA double strand breaks at telomeres. Expression of TRF2-S410A mutant fully rescued the recruitment of 53BP1 to telomeric breaks. These results suggest that TRF2 phosphorylation promotes association of TIN2 with the shelterin complex and regulates DNA repair at telomeres.
2023-03-11 | PXD035268 | Pride
Project description:Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. By targeting additional substrates at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified a novel interaction between PPM1D and the shelterin complex that protects telomeric DNA. In addition, confocal microscopy revealed that endogenous PPM1D colocalized with TRF2 at telomeres. Further, we found that ATR phosphorylated TRF2 at S410 after induction of DNA double strand breaks at telomeres and this modification increased after inhibition or loss of PPM1D. TRF2 phosphorylation stimulated its interaction with TIN2 both in vitro and at telomeres. Conversely, induced expression of PPM1D impaired localisation of TIN2 and TPP1 at telomeres. Finally, recruitment of the DNA repair factor 53BP1 to the telomeric breaks was strongly reduced after inhibition of PPM1D and was rescued by the expression of TRF2-S410A mutant. Our results suggest that TRF2 phosphorylation promotes the association of TIN2 within the shelterin complex and regulates DNA repair at telomeres.
2023-03-11 | PXD035273 | Pride