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SRP110248
Homo sapiens
30 Downloadable Samples
Illumina HiSeq 2000
Description
Small ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Publication Title
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
RNA localization is a regulatory mechanism that is conserved from bacteria to mammals. Yet, little is known about the mechanism and the logic that govern the distribution of RNA transcripts within the cell. Here we present a novel organ culture system, which enables the isolation of RNA specifically from NGF dependent re-growing peripheral axons of mouse embryo sensory neurons. In combination with massive parallel sequencing technology, we determine the sub-cellular localization of most transcripts in the transcriptome. We found that the axon is enriched in mRNAs that encode secreted proteins, transcription factors and the translation machinery. In contrast, the axon was largely depleted from mRNAs encoding transmembrane proteins, a particularly interesting finding, since many of these gene products are specifically expressed in the tip of the axon at the protein level. Comparison of the mitochondrial mRNAs encoded in the nucleus with those encoded in the mitochondria, uncovered completely different localization pattern, with the latter much enriched in the axon fraction. This discovery is intriguing since the protein products encoded by the nuclear and mitochondrial genome form large co-complexes. Finally, focusing on alternative splice variants that are specific to axonal fractions, we find short sequence motifs that are enriched in the axonal transcriptome. Together our findings shed light on the extensive role of RNA localization and its characteristics. Overall design: For each RNA sample, Spinal Cords\ DRGs were dissected from 40 E13.5 embryos and cultured for 48H. Total RNA was extracted from whole DRG and Peripheral axons. Poly-A enriched. In duplicates, using GAIIx. Read length - 80nt.
Publication Title
Subcellular transcriptomics-dissection of the mRNA composition in the axonal compartment of sensory neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The goal of this study is to uncover the changes in the transcriptome of sensory neurons of the liver kinase B1 (LKB1) knockout
Publication Title
Regulation of axonal morphogenesis by the mitochondrial protein Efhd1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Loss of CLP1 activity results in the accumulation of novel sets of small RNA fragments derived from aberrant processing of tyrosine pre-tRNA. Such tRNA fragments sensitize cells to oxidative stress-induced p53 activation and p53-dependent cell death. Overall design: 2 samples, Wt and Clp1(k/k), no replicates
Publication Title
CLP1 links tRNA metabolism to progressive motor-neuron loss.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Myeloid progenitors derived from antibiotic-treated mice have cell-intrinsic functional defects. In this microarray dataset, the transcriptomes of bone marrow myeloid progenitors from antibiotic-treated and control mice are compared.
Publication Title
Microbiota-dependent signals are required to sustain TLR-mediated immune responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
To study the effect of Prnp genetic ablation on different aspects of RNA metabolism, we performed RNA sequencing of the hippocampus of wild-type C57BL/6J, congenic B6.129-PrnpZH1/ZH1 and coisogenic C57BL/6J-PrnpZH3/ZH3 mice. We analyzed differential gene expression, exon usage and RNA editing. Overall design: RNA sequencing on hippocampus of wild-type C57BL/6 mice, congenic B6.129-PrnpZH1/ZH1 and coisogenic C57BL/6-PrnpZH3/ZH3 mice (3 month-old males, n=4 per genotype).
Publication Title
Strictly co-isogenic C57BL/6J-Prnp-/- mice: A rigorous resource for prion science.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
The Igf2 mRNA binding protein2/Imp2 was selectively deleted from adult mouse muscle; two phenotypes were observed: modestly decreased accrual of skeletal muscle mass after weaning and reduced wheel running activity but normal forced treadmill performance. Reduced voluntary activity occurs when fed a high fat diet but is normalized when consuming standard chow. The reduced muscle mass is due to diminished autocrine Igf2 production, reduced Akt1 activation, disinhibition of Gsk3a and reduced protein synthesis, without altered mTOR complex1 activity. The diet-dependent reduction in spontaneous exercise is accompanied by suboptimal muscle fatty acid oxidation, caused by reduced PPARa mRNA and protein, the former an Imp2 client. Nevertheless, in contrast to global Imp2 deficiency, muscle specific Imp2 inactivation does not alter glucose tolerance or the hypoglycemic effect of insulin. Imp2 deficiency in skeletal muscle reduces autocrine production of Igf2 and fiber growth and disorders nutrient metabolism so as to reduce voluntary physical activity. Overall design: The function of IMP2 in adult muscle has been investigated by creating the IMP2 muscle specific knockout mice. The metabolism of these mice at the whole body level, cellular lever, molecular level have been studied.
Publication Title
IMP2 Increases Mouse Skeletal Muscle Mass and Voluntary Activity by Enhancing Autocrine Insulin-Like Growth Factor 2 Production and Optimizing Muscle Metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Dynamic binding of transcription factors to DNA elements specifies gene expression and cell fate, in both normal physiology and disease. To date, our understanding of mammalian gene regulation has been hampered by the difficulty of directly measuring in vivo binding of large numbers of transcription factors to DNA. Here, we develop a high-throughput indexed Chromatin ImmunoPrecipitation (iChIP) method coupled to massively parallel sequencing to systematically map protein-DNA interactions. We apply iChIP to reconstruct the physical regulatory landscape of a mammalian cell, by building genome-wide binding maps for 29 transcription factors (TFs) and chromatin marks at four time points following stimulation of primary dendritic cells (DCs) with pathogen components. Using over 180,000 TF-DNA interactions in these maps, we derive an initial dynamic physical model of a mammalian cell regulatory network. Our data demonstrates that transcription factors vary substantially in their binding dynamics, genomic localization, number of binding events, and degree of interaction with other factors. Further, many of the TF-DNA interactions at stimulus-activated genes are established during differentiation and maintained in a poised state. Functionally, the TFs are organized in a hierarchy of different types: Cell differentiation factors bind most of the genes and remain largely unchanged during the stimulation. A second set of TFs bind already in the un-stimulated and preferentially target induced genes. A third set consists of TF that bind mainly after the stimuli and target specific gene functions. Together these factors determine the magnitude and timing of stimulus induced gene expression. Our method, which allowed us to map routinely temporal binding profiles of dozens of TFs, provides a foundation for future understanding of the mammalian regulatory code. Overall design: A study of dynamic binding of transcription factors in an immune cell following pathogen stimulation
Publication Title
A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Publication Title
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Publication Title
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part, Cell line
View Samples