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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from Top2β KO cells as well ICRF-193 treatment of in vitro derived neurons and cortical glutamatergic neurons

ABSTRACT: Expression profiling of from Top2β knokout and ICRF-193 treated neurons reveals a significant number of genes that are transcriptionally deregulated Gene expression in the Top2β knocnout ES, NP and TN stages of stem cell differention to the corresponidng wild type cells. In vitro derived neurons and cortical glutamatergic neurons were either treated with DMSO or ICRF-193 and were compared to reveal differentially expressed genes.

ORGANISM(S): Mus musculus

SUBMITTER: Dirk Schuebeler

PROVIDER: E-GEOD-27245 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.

Tiwari Vijay K VK Burger Lukas L Nikoletopoulou Vassiliki V Deogracias Ruben R Thakurela Sudhir S Wirbelauer Christiane C Kaut Johannes J Terranova Remi R Hoerner Leslie L Mielke Christian C Boege Fritz F Murr Rabih R Peters Antoine H F M AH Barde Yves-Alain YA Schübeler Dirk D

Proceedings of the National Academy of Sciences of the United States of America 20120402 16

Topoisomerases are essential for DNA replication in dividing cells, but their genomic targets and function in postmitotic cells remain poorly understood. Here we show that a switch in the expression from Topoisomerases IIα (Top2α) to IIβ (Top2β) occurs during neuronal differentiation in vitro and in vivo. Genome-scale location analysis in stem cell-derived postmitotic neurons reveals Top2β binding to chromosomal sites that are methylated at lysine 4 of histone H3, a feature of regulatory regions ...[more]

PMID: 22474351

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Topoisomerase IIbeta occupies H3K4 methylated sites and regulates neuronal survival via repression of the neurotrophin receptor p75

Project description:This SuperSeries is composed of the following subset Series: GSE27245: Expression data from Top2Î² KO cells as well ICRF-193 treatment of in vitro derived neurons and cortical glutamatergic neurons GSE27246: Top2Î² ChIP-chip Refer to individual Series

2012-05-01 | E-GEOD-27247 | biostudies-arrayexpress

Gene regulation and priming by Topoisomerase IIα in embryonic stem cells [RNA-Seq]

Project description:Topoisomerases are essential for resolving topological problems in the genome, while their function in gene regulation, especially during cellular differentiation, remains unknown. We reveal that the expression of two Topo II isoforms, Top2a and Top2ß, is characteristic of dividing and postmitotic tissues, respectively. In embryonic stem cells, Top2a preferentially binds to promoters embedded in an active chromatin environment. Inhibition of Top2a activity results in misregulation of target gene expression that accompanies accumulation of double-strand breaks. Common targets of Top2a and Top2ß are housekeeping genes while their unique targets are involved in proliferation/pluripotency and neurogenesis, respectively. Moreover, a subset of Top2a targets exhibit bivalent chromatin state that is resolved upon differentiation concomitant with their activation and occupancy by Top2ß, a feature further observed for long genes. These findings suggest that Top2a not only contributes to stem cell transcriptome regulation but may also prime developmental genes for subsequent activation upon differentiation. mRNA profiles of DMSO and ICRF-193 treated mESCs were generated by deep sequencing in triplicates. ICRF-193 is a well established catalytic inhibitor of Topoisomerase II, hence, we used ICRF-193 to the elucidate role of Top2a catalytic activity on transcription by genome wide transcription profiling.

2013-10-10 | E-GEOD-46066 | biostudies-arrayexpress

Gene regulation and priming by Topoisomerase II? in embryonic stem cells [FAIRE-Seq]

2013-10-10 | E-GEOD-49141 | biostudies-arrayexpress

Gene regulation and priming by Topoisomerase IIÎ± in embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-10-10 | E-GEOD-46070 | biostudies-arrayexpress

Expression data from Top2β KO cells as well ICRF-193 treatment of in vitro derived neurons and cortical glutamatergic neurons

Project description:Expression profiling of from Top2β knokout and ICRF-193 treated neurons reveals a significant number of genes that are transcriptionally deregulated

2012-05-02 | GSE27245 | GEO

DNA damage hotspots for the Top2i "ICRF193"

Project description:In our project we are using the Top2 inhibitor, ICRF-193, in order to induce damage in NIH3T3 MEFs. We report the high-throughput identification of genomic hotspots for damage induction by ICRF-193, using γH2AX as a marker. We find that ICRF-193 primarily induces damage in repetitive sequences, which are known to reside in regions of heterochromatin, with a very small portion of damaged sites residing in regions of active genes in euchromatin. Overall, this study provides evidence that catalytic inhibition of Top2 enzymes by ICRF-193, leads to induction of damage in the nuclear sub-compartments of heterochromatin.

2024-04-17 | GSE256090 | GEO

DNA binding factors shape the mouse methylome at distal regulatory regions [RNA_seq]

Project description:To gain insights into the interplay between DNA methylation and gene regulation we generated a basepair resolution reference map of the mouse methylome in stem cells and neurons. High genome coverage allowed for a novel quantitative analysis of local methylation states, which identified Low Methylated Regions (LMR) with an average methylation of 30%. These regions are evolutionary conserved, reside outside of CpG islands and distal to promoters. They represent regulatory regions evidenced by their DNaseI hypersensitivity and chromatin marks of enhancer elements. LMRs are occupied by transcription factors (TF) and their reduced methylation requires TF binding while introduction of TF binding sites creates LMRs de novo. This dependency on TF activity is further evident when comparing the methylomes of embryonic stem cells and derived neuronal cells. LMRs present in both cell types are occupied by broadly expressed factors, while LMRs present at only one state are occupied by cell-type specific TFs. Methylome data can thus enhance the prediction of occupied TF binding sites and identification of active regulatory regions genome-wide. Our study provides reference methylomes for the mouse at two cell states, identifies a novel and highly dynamic feature of the epigenome that defines distal regulatory elements and shows that transcription factor binding dynamically shapes mammalian methylomes. RNA_sequencing of mouse embryonic stem (ES) cells and derived neuronal progenitors (NP).

2011-12-22 | E-GEOD-30280 | biostudies-arrayexpress

Genomic prevalence of heterochromatic H3K9me2 and transcription do not discriminate pluripotent from terminally differentiated cells (RNA-seq)

Project description:Cellular differentiation entails reprogramming of the transcriptome from a pluripotent to a unipotent fate. This process was suggested to coincide with a global increase of repressive heterochromatin, which results in a reduction of transcriptional plasticity and potential. Here we report the dynamics of the transcriptome and an abundant heterochromatic histone modification, dimethylation of histone H3 at lysine 9 (H3K9me2), during neuronal differentiation of embryonic stem cells. In contrast to the prevailing model, we find H3K9me2 to occupy over 50% of chromosomal regions already in stem cells. Marked are most genomic regions that are devoid of transcription and a subgroup of histone modifications. Importantly, no global increase occurs during differentiation, but discrete local changes of H3K9me2 particularly at genic regions can be detected. Mirroring the cell fate change many genes show altered expression upon differentiation. Quantitative sequencing of transcripts reveals however that the total number of active genes is equal between stem cells and several tested differentiated cell types. Together, these findings reveal high prevalence of a heterochromatic mark in stem cells and challenge the model of low abundance of epigenetic repression and resulting global transcription in stem cells. Instead cellular differentiation entails local rather than global changes in epigenetic repression and transcriptional activity. Our dataset comprises of 2 ChIP-seq samples using chromatin from embryonic stem (ES) cells and derived terminal neurons (TN) which was immunoprecipitated, using antibodies against H3K27me3 and H3K4me2. For the same cells we generated H3K9me2 ChIP-chip samples in biological replicates. For ES cells, neurons and mouse embryonic fibroblasts (MEFs) we generated biological replicates of RNA-seq data.

2011-06-21 | E-GEOD-27843 | biostudies-arrayexpress

Mus musculus

Project description:Expression data from Top2β KO cells as well ICRF-193 treatment of in vitro derived neurons and cortical glutamatergic neurons

| PRJNA141813 | ENA

DNA binding factors shape the mouse methylome at distal regulatory regions [strand-specific-RNA-seq]

Project description:To gain insights into the interplay between DNA methylation and gene regulation we generated a basepair resolution reference map of the mouse methylome in stem cells and neurons. High genome coverage allowed for a novel quantitative analysis of local methylation states, which identified Low Methylated Regions (LMR) with an average methylation of 30%. These regions are evolutionary conserved, reside outside of CpG islands and distal to promoters. They represent regulatory regions evidenced by their DNaseI hypersensitivity and chromatin marks of enhancer elements. LMRs are occupied by transcription factors (TF) and their reduced methylation requires TF binding while introduction of TF binding sites creates LMRs de novo. This dependency on TF activity is further evident when comparing the methylomes of embryonic stem cells and derived neuronal cells. LMRs present in both cell types are occupied by broadly expressed factors, while LMRs present at only one state are occupied by cell-type specific TFs. Methylome data can thus enhance the prediction of occupied TF binding sites and identification of active regulatory regions genome-wide. Our study provides reference methylomes for the mouse at two cell states, identifies a novel and highly dynamic feature of the epigenome that defines distal regulatory elements and shows that transcription factor binding dynamically shapes mammalian methylomes. Strand specific expression profiling by high throughput sequencing.

2011-12-15 | E-GEOD-31385 | biostudies-arrayexpress

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