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GSE14088
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificity established? Here we report that, like UBE2M (also known as UBC12), the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro and in vivo. Biochemical and structural analyses indicate how plasticity of hydrophobic E1-E2 interactions and E1 conformational flexibility allow one E1 to charge multiple E2s. The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities. Together, these studies reveal the molecular basis for and functional importance of hierarchical expansion of the NEDD8 conjugation system in establishing selective CRL activation.
Publication Title
E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here, we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature, and nerves are specified and the musculoskeletal system of the limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore-limb and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which tampers off at later time points. Among 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that correlate with functional programs during limb development and are likely to provide new insights into specific tissue patterning processes. Here we provide for the first time, a comprehensve analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.
Publication Title
Global gene expression analysis of murine limb development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin de-compaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity, and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina, and die of cardiac malfunction. Chromatin de-compaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.
Publication Title
Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HMGN (high mobility group N) is a family of intrinsically disordered nuclear proteins that binds to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family.
Publication Title
Effects of HMGN variants on the cellular transcription profile.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emergning as key regulatory proteins with great promise as therapeutic agents for bone disorders. Until recently Sost and its paralog Sostdc1 have been described as growth factors with highly restricted expression in the adult where Sost was assumed 'osteocyte-' and Sostdc1 'kidney-' specific. Here we show that these two proteins emerged throgh ancestral genome duplication and their expression patterns have diverged to span complimentary domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme.
Publication Title
Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 218 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
To understand the molecular mechanisms of human lung macrophage development, function, and role in BPD pathogenesis, we conducted a clinical study using isolated tracheal aspirate macrophages from intubated preterm infants born before 30 wk gestation. One hundred twenty-eight patients intubated for respiratory distress syndrome and surfactant administration were consented for the study.
Publication Title
Transcriptional profiling of lung macrophages identifies a predictive signature for inflammatory lung disease in preterm infants.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The transcription factor c-MYC intron binding protein 1 (MIBP1) binds to various genomic regulatory regions, including intron 1 of c-MYC. This factor is highly expressed in post-mitotic neurons in the fetal brain and may be involved in various biological steps, such as neurological and immunological processes. In this study, we globally characterized the transcriptional targets of MIBP1 and proteins that interact with MIBP1. Microarray hybridization followed by Gene Set Enrichment Analysis revealed that genes involved in the pathways downstream of MYC, NF-B, and TGF- were downregulated when HEK293 cells stably overexpressed MIBP1. In silico transcription factor binding site analysis of the promoter regions of these downregulated genes showed that the NF-B binding site was the most overrepresented. The upregulation of genes known to be in the NF-B pathway after the knockdown of endogenous MIBP1 in HT1080 cells supports the view that MIBP1 is a downregulator of the NF-B pathway. We also confirmed the binding of the MIBP1 to the NF-B site. By immunoprecipitation and mass spectrometry, we detected O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT) as a prominent binding partner of MIBP1. Analyses using deletion mutants revealed that a 154-amino acid region of MIBP1 was necessary for its OGT binding and O-GlcNAcylation. A luciferase reporter assay showed that NF-B-responsive expression was repressed by MIBP1, and stronger repression by MIBP1 lacking the 154-amino acid region was observed. Our results indicate that the primary effect of MIBP1 expression is the downregulation of the NF-B pathway, and that this effect is attenuated by O-GlcNAc signaling.
Publication Title
Genome-wide repression of NF-κB target genes by transcription factor MIBP1 and its modulation by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Snail is a transcriptional repressor, which induces epithelial-mesenchymal transition. However, overall functions of Snail remain to be elucidated. This microarray was performed to investigate the influence of Snail expression on mRNA transcription levels in a lung adenocarcinoma cell line, II-18.
Publication Title
Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To realize cell transplantation therapy for Parkinson's disease (PD), the grafted neurons should be integrated into the host neuronal circuit in order to restore the lost neuronal function. Here, using wheat germ agglutinin-based trans-synaptic tracing, we show that integrin 5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons from the mouse experiments. Additionally, we found that integrin 51 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin 51. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administrated rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD.
Publication Title
Estradiol Facilitates Functional Integration of iPSC-Derived Dopaminergic Neurons into Striatal Neuronal Circuits via Activation of Integrin α5β1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Publication Title
NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism.
Sample Metadata Fields
Specimen part
View Samples