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

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Dirk Schuebeler

PROVIDER: E-GEOD-27247 | 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

Similar Datasets

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 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.

2012-05-01 | E-GEOD-27245 | 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

Gene regulation and priming by Topoisomerase IIÎ± in embryonic stem cells [ChIP-chip]

Project description:Topoisomerases are essential for resolving topological problems in the genome, while their function in gene regulation, especially during cellular differentiation, remains elusive/unknown. We reveal that the expression of two Topo II isoforms, Top2Î± and Top2Î², is characteristic of dividing and postmitotic tissues, respectively. In embryonic stem cells, Top2Î± preferentially binds to promoters embedded in an active chromatin environment. Inhibition of Top2Î± activity results in misregulation of target gene expression that accompanies accumulation of double-strand breaks. Common targets of Top2Î± and Top2Î² are housekeeping genes while their unique targets are involved in proliferation/pluripotency and neurogenesis (Can we say this as this might be because we are driving neurons from ES cells), respectively. Moreover, a small subset of Top2Î± targets exhibit bivalent chromatin state that is resolved upon differentiation concomitant with their activation and occupancy by Top2Î², a feature further observed for large lengthlong genes. These findings suggest that Top2Î± not only contributes to stem cell transcriptome regulation but may also prime developmental genes for subsequent activation by Top2Î². Chromatin IP was performed with Top2Î± antibodies in WT ES cells and hybridized to custom designed tiling array.

2013-10-10 | E-GEOD-45890 | biostudies-arrayexpress

Top2Î² ChIP-chip

Project description:Chromatin IP was performed with Top2Î² antibodies in WT neurons and hybridized to custom designed tiling array. HD 2.1 (custom- made)

2012-05-01 | E-GEOD-27246 | 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]

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-49141 | biostudies-arrayexpress

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

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-27724 | biostudies-arrayexpress

Role of JNK during Stem Cell Differentiation

Project description:This SuperSeries is composed of the following subset Series: GSE25529: Expression data from DMSO and SP600125 treated neurons GSE25532: NF-Y recruits JNK to Chromatin during Stem Cell Differentiation Refer to individual Series

2011-12-18 | E-GEOD-25533 | biostudies-arrayexpress

Role of REST during neuronal differentiation

Project description:This SuperSeries is composed of the following subset Series: GSE27114: Expression data from REST knock-out versus REST wild type cells during in vitro neurogenesis GSE27148: A comparative epigenomics approach reveals REST as a mediator of Polycomb reprogramming during neuronal differentiation Refer to individual Series

2012-09-04 | E-GEOD-27341 | biostudies-arrayexpress

Expression data from REST knock-out versus REST wild type cells during in vitro neurogenesis

Project description:While changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. We developed a computational model on the premise that transcription factors (TFs) direct dynamic chromatin changes during cell fate decisions. When applied to a neurogenesis paradigm, this approach predicted the TF REST as a determinant of gain of Polycomb-mediated H3K27me3 in neuronal progenitor cells. We prove this prediction experimentally by showing that the absence of REST causes loss of H3K27me3 at target promoters in trans at the same cellular state. Moreover, promoter fragments containing a REST binding site are sufficient to recruit H3K27me3 in cis, while deletion of their REST site results in loss of H3K27me3. These findings illustrate that computational modeling can systematically identify TFs that regulate chromatin dynamics genome-wide. Local determination of Polycomb activity by REST exemplifies such TF based regulation of chromatin. Expression profiling of REST knock-out (RESTko) versus REST wildtype (RESTwt) or REST heterozygous knock-out (RESThet) cells at three stages of in vitro neuronal differentiation. RESTko and RESTwt/RESThet embryonic stem (ES) cells were differentiated to terminal neurons (TN) via a defined neuronal progenitor (NP) state. Three biological replicates (suffixes a to c).

2012-09-04 | E-GEOD-27114 | biostudies-arrayexpress

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