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Mus musculus
29 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anti-cancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling towards senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development.
Publication Title
DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The hypothalamus has recently emerged as a key regulator of metabolism and aging in mammals. We have examined the impact of targeted disruption of hypothalamic hypophysiotropic peptide: Growth Hormone-releasing Hormone (GHRH) in mice on longevity, and the putative mechanisms of delayed aging. GHRH knockout (KO) mice are remarkably long-lived and in comparison to genetically normal (wild type) animals exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of GH. While these effects overlap with those of caloric restriction (CR), we show that effects of CR and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity.
Publication Title
Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Expression profiling of resting B cells to classify active and silent genes based on expression levels Overall design: 4 biological replicates of mRNA extracted from freshly purified mouse CD43 negative resting B cells
Publication Title
The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Polycomb repressive complex 2 (PRC2) maintains developmental regulator genes in a repressed state through methylation of histone H3 at lysine 27 (H3K27me3) and is necessary for cell differentiation. We and others have previously found that the PRC2 subunit Suz12 interacts with RNA in vitro and other studies have shown that Ezh2 and Jarid2 also possess RNA binding function. The interaction of PRC2 with RNA has been suggested to regulate PRC2 targeting or enzymatic activity, but the RNAs directly bound by PRC2 in cells, and the role of each PRC2 RNA binding subunit, remain unclear. We have used different CLIP techniques, which use UV-crosslinking to allow detection of direct Suz12-RNA interactions as they occur in living mouse ES cells. Suz12 binds nascent RNA and has a preference for interaction with the 3'UTR, showing it does have binding specificity in cells. RNAs bound by Suz12 at the 3'UTR encode developmental regulator genes. Suz12 remains bound to RNA upon deletion of Ezh2 or Jarid2 showing that it binds RNA independently of other PRC2 subunits. We also show that binding of Suz12 to RNA or chromatin is mutually inhibitory. Although Ezh2 and Jarid2 also bind RNA, Ezh2 and Jarid2 deletion causes an increase in Suz12 RNA binding, without changing its specificity, which reflects the loss of Suz12 from chromatin. Similarly, disruption of Suz12-RNA interactions by RNA polymerase II inhibition or RNase treatment increases Suz12 binding to chromatin. These results therefore suggest that Suz12 acts as an RNA sensor, binding to the 3'UTR of nascent RNAs and modulating the interaction of PRC2 with chromatin. Overall design: Total RNAseq libraires from of Mus musculus Ezh2 fl/fl Stem Cells after and before Tamoxifen treatment.Up to three replicates per condition
Publication Title
The interaction of PRC2 with RNA or chromatin is mutually antagonistic.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
80% of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding. Depletion of CP190 reduces the number of Gcn5 binding sites and binding strength to chromatin. Binding dependency was further supported by Gcn5 mediated co-precipitation of CP190 Overall design: RNA-seq expression profiles of drosophila S2 mRNA after depletion of CP190 and Gcn5
Publication Title
Chromatin binding of Gcn5 in Drosophila is largely mediated by CP190.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Understanding the physiological relevance of structures in mammalian mRNAs remains elusive, especially considering the global unfolding of mRNA structures in eukaryotic organisms recently examined, as well as the decade-long observation that mRNAs generally seem no more likely than random sequences to be stably folded. Here we show that RNA secondary structures, mostly weak and close-to-random, facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. Folding of these 3'-end structures also enhances mRNA stability. Global structure probing shows that 3'-end regions are indeed folded in cells despite substantial unfolding of PAS-upstream regions. Analyses of thousands of ectopically expressed variants prove that folding both enhances processing and increases stability. Mutagenesis of a genomic locus further implicates structure-controlled processing in regulating neighboring gene expression. These results reveal widespread roles for RNA structure in mammalian mRNA biogenesis and metabolism. Overall design: This series includes 8 samples designed to measure the efficiency of 3'' end processing from a reporter library expressed in HEK293T cells and HeLa cells, in steady state or in nascent RNAs (by 4sU labeling and capture).
Publication Title
Widespread Influence of 3'-End Structures on Mammalian mRNA Processing and Stability.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 2 Downloadable Samples
- Illumina Genome Analyzer
Description
Small endogenous C. elegans RNAs from L4 and young adult worms were prepared for sequencing using a protocol derived from Batista et al., (2008) and Lau et al. (2001). The small-RNA libraries were constructed using a method that does not require a 5' monophosphate (called 5' monophosphate-independent method, Ambros et al., 2003) to profile secondary siRNAs that have 5' triphosphorylated G. All preprocessed small-RNA reads were mapped to genome (ce6), allowing no mismatches. After excluding miRNAs, 21U RNAs, rRNAs, and other structural ncRNAs, the remaining reads were classified as 22G RNAs, 26G RNAs, and other siRNAs, based on their length and 5' terminal nucleotide. Overall design: Small-RNA libraries were sequenced in L4 and young adult stages in C.elegans.
Publication Title
Long noncoding RNAs in C. elegans.
Sample Metadata Fields
Cell line, Subject
View Samples
GSE103199- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show when depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
Publication Title
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Sample Metadata Fields
Cell line
View Samples