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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Linking oncogenic signaling to transcriptional changes by epigenomic data in a cell line model of human glioblastoma

ABSTRACT: We present a computational method for building a regulatory network from global phosphoproteomic and transcription profiling data. To recover the critical missing links between signaling events and transcriptional responses, we relate changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). Genome-wide DNase I hypersensitivity followed by sequencing (DNase-Seq) to measure chromatin accessibility in a cell line derived from the U87MG glioblastoma cell line to express high level of EGFRvIII (U87H; 2 million copies of EGFRvIII per cell) and a control cell line expressing kinase dead EGFRvIII (U87DK; 2 million kinase dead EGFRvIII per cell). A prediction from the computational method, the transcriptional co-regulator p300, was experimentally validated by chromatin immunoprecipitation followed by sequencing (ChIP-Seq).

ORGANISM(S): Homo sapiens

SUBMITTER: Shao-shan Huang

PROVIDER: E-GEOD-36900 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

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Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1 (ChIP-Seq)

Project description:In HuntingtonM-bM-^@M-^Ys disease (HD), polyglutamine expansions in the huntingtin (Htt) protein cause subtle changes in cellular functions that, over-time, lead to neurodegeneration and death. Studies have indicated that activation of the heat shock response can reduce many of the effects of mutant Htt in disease models, suggesting that the heat shock response is impaired in the disease. To understand the basis for this impairment, we have used genome-wide chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) to examine the effects of mutant Htt on the master regulator of the heat shock response, HSF1. We find that, under normal conditions, HSF1 function is highly similar in cells carrying either wild-type or mutant Htt. However, polyQ-expanded Htt severely blunts the HSF1-mediated stress response. Surprisingly, we find that the HSF1 targets most affected upon stress are not directly associated with proteostasis, but with cytoskeletal binding, focal adhesion and GTPase activity. Our data raise the intriguing hypothesis that the accumulated damage from life-long impairment in these stress responses may contribute significantly to the etiology of Huntington's disease. ChIP-Seq experiments for HSF-1 were performed in striatal cells that express either wild-type or mutant Htt using ChIP-Seq technology under normal (33M-BM-0C) and heat shock (42M-BM-0C for six hours) conditions. The cells were crosslinked with 1% formaldehyde and immunoprecipitated using antibody sc-9144 (Santa Cruz Biotech) for HSF-1. Sequencing was performed using the Illumina Genome Analyzer II.

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Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1

Project description:This SuperSeries is composed of the following subset Series: GSE38000: Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1 (ChIP-Seq) GSE38001: Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1 (mRNA) Refer to individual Series

2012-06-18 | E-GEOD-38002 | biostudies-arrayexpress

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Project description:To determine whether insertion of a single amino acid had an effect on Glucocorticoid receptor (GR) occupancy, we performed ChIP-seq of GRalpha and GRgamma in the same U2OS osteosarcoma cell lines, upon glucocorticoid treatment. These assays are also part of submission E-MTAB-2955

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Project description:To identify the sequences responsible for recruitment of Glucocorticoid receptor (GR) to individual loci, we performed ChIP-seq and ChIP-exo that combines chromatin immunoprecipitation with an exonuclease digestion step. We performed these experiments in three cell lines : IMR90 (ATTC:CCL-186), U2OS osteosarcoma cell lines, K562 (ATCC:CCL243), upon glucocorticoid treatment. The U2OS assays are the same as those in E-MTAB-2731.

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2012-02-10 | E-GEOD-33653 | biostudies-arrayexpress

Identification of in vivo binding sites of human GFP-tagged C2H2-ZF proteins

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H3K4me3 modification profiling of Huntingtons disease and control human post-mortem prefrontal cortex brain samples

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2015-12-14 | E-GEOD-68952 | biostudies-arrayexpress

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