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SRP073194
Mus musculus
46 Downloadable Samples
Illumina HiSeq 2000
Description
The tumor suppressor p53 is a transcription factor that controls the response to stress. Here, we dissected the transcriptional programs triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. p53 recruitment at these sites was mainly mediated through protein-protein or protein-chromatin interactions and, only for a small fraction, through recognition of the 20 base-pair p53 consensus motif. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. p53 also targeted unmarked distal sites devoid of activation marks, at which binding was prevalently driven by recognition of the consensus motif. At all sites, our data highlighted a functional role for the canonical, unsplit consensus element, but did not provide evidence for p53 recruitment by split motifs. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 re-activation and tumor regression. Overall design: Total RNA profiling of gene expression in Eµ-myc lymphomas following p53 restoration by Illumina sequencing
Publication Title
Genome-wide analysis of p53-regulated transcription in Myc-driven lymphomas.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 56 Downloadable Samples
- Illumina HiSeq 2000
Description
Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc's association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response. Overall design: Time course profiling of 4sU-labeled and total RNA upon Myc activation in 3T9-MycER mouse fibroblasts
Publication Title
Integrative analysis of RNA polymerase II and transcriptional dynamics upon MYC activation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of YAP and Myc induced in quiescent and confluent 3T9 fibroblasts Overall design: RNAseq analysis of YAP and Myc induced in quiescent and confluent 3T9 fibroblasts
Publication Title
Transcriptional integration of mitogenic and mechanical signals by Myc and YAP.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Tumors driven by activation of the transcription factor Myc generally show oncogene addiction. However, the gene-expression programs that depend upon sustained Myc activity in those tumors remain unknown. We have addressed this issue in a model of liver carcinoma driven by a reversible tet-Myc transgene, combining gene expression profiling with the mapping of Myc and RNA Polymerase II on chromatin. Switching off the oncogene in advanced carcinomas revealed that Myc is required for the continuous activation and repression of distinct sets of genes, constituting no more than half of those deregulated during tumor progression, and an even smaller subset of all Myc-bound genes. We further showed that a Myc mutant unable to associate with the co-repressor protein Miz1 is defective in the initiation of liver tumorigenesis. Altogether, our data provide the first detailed analysis of a Myc-dependent transcriptional program in a fully developed carcinoma, revealing that the critical effectors of Myc in tumor maintenance must be included within defined subsets (ca. 1,300 each) of activated and repressed genes. Overall design: RNAseq samples of control liver (n=11), tet-Myc tumors (n=16), tet-Myc tumors with short-term Myc inactivation (n=8), tet-MycVD tumors (n=11)
Publication Title
Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
The hst3hst4 strain (FY background) has the HST3 and HST4 genes, encoding putative NAD-dependent deacetylases that regulate histone 3 K56 acetylation, deleted. Expression profiling using Affymetrix microarrays was used to assess the change in the gene expression in this strain in comparison to wild-type under normal growth conditions.
Publication Title
Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
Publication Title
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
Publication Title
The l1-l2 regularization framework unmasks the hypoxia signature hidden in the transcriptome of a set of heterogeneous neuroblastoma cell lines.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
MicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -microRNAome - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3 untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
Publication Title
Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 29 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
Publication Title
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The essential thiol antioxidant, glutathione (GSH) is recruited into the nucleus of mammalian cells early in cell proliferation, suggesting a key role of the nuclear thiol pool in cell cycle regulation. However, the functions of nuclear GSH (GSHn) and its integration with the cytoplasmic GSH (GSHc) pools in whole cell redox homeostasis and signaling are unknown. Here we show that GSH is recruited into the nucleus early in cell proliferation in Arabidopsis thaliana, confirming the requirement for localization of GSH in the nucleus as a universal feature of cell cycle regulation.
Publication Title
Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.
Sample Metadata Fields
Treatment
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