A high resolution analyis of c-Myc-regulated gene expression dynamics.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE20550 | GEO | 2011/11/21
SECONDARY ACCESSION(S): PRJNA125309
REPOSITORIES: GEO
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Project description:We previously described the use of a spotted oligonucleotide array to identify the mir-17 cluster as a direct transcriptional target of Myc. In order to determine whether Myc regulates additional miRNAs, we produced custom microarrays with an expanded set of probes capable of assaying the expression of 313 human miRNAs and 233 mouse miRNAs. miRNA expression was assayed in a murine model of Myc-induced B cell lymphoma. In this system, bone marrow from p53-/- mice is infected with a retrovirus that produces a Myc-estrogen receptor fusion protein (MycER). Infected cells form polyclonal B cell lymphomas in the presence of 4-hydroxytamoxifen (4-OHT), which activates the MycER fusion protein. RNA from subcutaneous tumors with high Myc activity (animals treated continuously with 4-OHT) and low Myc activity (animals in which 4-OHT was withdrawn after tumor formation) was analyzed. Keywords: Dose Response
2007-12-05 | GSE9104 | GEO
Project description:We previously described the use of a spotted oligonucleotide array to identify the mir-17 cluster as a direct transcriptional target of Myc. In order to determine whether Myc regulates additional miRNAs, we produced custom microarrays with an expanded set of probes capable of assaying the expression of 313 human miRNAs and 233 mouse miRNAs. miRNA expression was assayed in a murine model of Myc-induced B cell lymphoma. In this system, bone marrow from p53-/- mice is infected with a retrovirus that produces a Myc-estrogen receptor fusion protein (MycER). Infected cells form polyclonal B cell lymphomas in the presence of 4-hydroxytamoxifen (4-OHT), which activates the MycER fusion protein. RNA from subcutaneous tumors with high Myc activity (animals treated continuously with 4-OHT) and low Myc activity (animals in which 4-OHT was withdrawn after tumor formation) was analyzed. Keywords: Dose Response RNA from 2 subcutaneous MycER tumors with high Myc activity (animals treated continuously with 4-OHT) and 2 tumors with low Myc activity (animals in which 4-OHT was withdrawn after tumor formation) was analyzed.
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Project description:Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progr 4 different experimental conditions were analyzed: MYC-ER 4-OHT treated versus MYC-ER ctr-treated (EtOH), MYC-ER V394D 4-OHT treated versus MYC-ER V394D ctr-treated; 3 biological replicates for every condition.
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Project description:In this work, we aimed at studying the impact of microRNAs on antiviral responses, using inducible deletion of one or two copies of Dicer1 (in Dicer-floxed x EsrCRE+ MEFs). Unexpectedly, we discovered that Cre-ERT activation by hydroxytamoxifen (OHT) alone, independent of Dicer1 deletion, had a strong impact on antiviral responses. These microarrays were performed on SV40 immortalized Dicer1 fl/fl EsrCRE+ MEFs, Dicer1 fl/wt EsrCRE+ MEFs, 96 h after initial OHT treatment, and SV40 immortalized Dicer1 wt/wt EsrCRE+ MEFs, Dicer1 wt/wt EsrCRE-neg MEFs (Wild Type MEFs), 48 h after initial OHT treatment. These analyses revealed the strong induction of several antiviral genes (Rsad2, Cxcl10...), following Cre-ERT activation. SV40 immortalized mouse embryonic fibroblasts from various genotypes were stimulated 24h with 500nM hydroxytamoxifen, and further expanded for 24 or 72h. Each sample was analyzed on Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray Each sample is in simplicate - no biological replicates; sample 1-4 were processed/analyzed on a different microarray slide to 5-8 (different day/operator)
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