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Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network

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

ORGANISM(S): Mus musculus

SUBMITTER: Pasquale Laise

PROVIDER: E-GEOD-76292 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.

Signaroldi Elena E Laise Pasquale P Cristofanon Silvia S Brancaccio Arianna A Reisoli Elisa E Atashpaz Sina S Terreni Maria Rosa MR Doglioni Claudio C Pruneri Giancarlo G Malatesta Paolo P Testa Giuseppe G

Nature communications 20160229

Malignant gliomas constitute one of the most significant areas of unmet medical need, owing to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent net ...[more]

PMID: 26923714

Similar Datasets

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network [RNA-Seq]

Project description:Malignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Transcriptomic analysis of two different stages of gliomagenesis

2016-03-02 | E-GEOD-76291 | biostudies-arrayexpress

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network [ChIP-Seq]

Project description:Malignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Analysis of H3K27me3 distribition in two different stages of gliomagenesis

2016-03-02 | E-GEOD-76289 | biostudies-arrayexpress

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.

Project description:Malignant gliomas constitute one of the most significant areas of unmet medical need, owing to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We find that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated with invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a critical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signalling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signalling.

| S-EPMC4773478 | biostudies-literature

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-03-02 | GSE76292 | GEO

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network [ChIP-Seq]

2016-03-02 | GSE76289 | GEO

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network [RNA-Seq]

2016-03-02 | GSE76291 | GEO

Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network

Project description:Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network

| PRJNA306825 | ENA

Sequence database choice significantly affects taxonomic and functional metaproteomic results in gut microbiota studies

Project description:Elucidating the role of gut microbiota in physiological and pathological processes has recently emerged as a key research aim in life sciences. In this respect, metaproteomics (the study of the whole protein complement of a microbial community) can provide a unique contribution by revealing which functions are actually being expressed by specific microbial taxa. However, its wide application to gut microbiota research has been hindered by challenges in data analysis, especially related to the choice of the proper sequence databases for protein identification. Here we present a systematic investigation of variables concerning database construction and annotation, and evaluate their impact on human and mouse gut metaproteomic results. We found that both publicly available and experimental metagenomic databases lead to the identification of unique peptide assortments, suggesting parallel database searches as a mean to gain more complete information. Taxonomic and functional results were revealed to be strongly database-dependent, especially when dealing with mouse samples. As a striking example, in mouse the Firmicutes/Bacteroidetes ratio varied up to 10-fold depending on the database used. Finally, we provide recommendations regarding metagenomic sequence processing aimed at maximizing gut metaproteome characterization, and contribute to identify an optimized pipeline for metaproteomic data analysis.

2016-10-10 | PXD004039 | Pride

The heme-responsive PrrH sRNA regulates Pseudomonas aeruginosa pyochelin gene expression

Project description:Pseudomonas aeruginosa is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, P. aeruginosa expresses the PrrF1 and PrrF2 small regulatory RNAs (sRNAs), which post-transcriptionally repress expression of non-essential iron-containing proteins thus sparing this nutrient for more critical processes.The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH. While the functions of PrrF1 and PrrF2 have been studied extensively, the role of PrrH in P. aeruginosa physiology and virulence is not well understood. In this study, we performed transcriptomic and proteomic studies to identify the PrrH regulon.

2023-08-11 | PXD040948 | Pride

Polycomb preferentially targets stalled promoters of coding and non-coding transcripts

Project description:The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modification of target loci. Despite our broad knowledge about composition and enzymatic activities of the protein complexes involved, our understanding still lacks important mechanistic detail and a comprehensive view on target genes. In this study, we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide detection of transcription start sites (TSSs) to identify and analyze thousands of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell line. In addition to finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic PcG-binding sites coinciding with non-annotated transcription start sites. Interestingly, this set includes previously unknown promoters for primary transcripts of microRNA genes, thereby expanding the scope of Polycomb control to non-coding RNAs essential for development, apoptosis and growth. Chromatin from S2 cells was immunoprecipitated using antibodies against Pc, Ph, Psc, Trx-C or H3K4me3. In parallel, we isolated RNA from S2 cells and generated global gene expression profiles by RNA-seq. We also surveyed the Drosophila genome for yet non-annotated transcription start sites (TSSs) using a newly adapted protocol for Illumina sequencing (termed 5M-bM-^@M-^Y-MACE) with RNA isolated from S2 cells and embryos.

2010-12-21 | E-GEOD-24521 | biostudies-arrayexpress

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