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E-MEXP-1028
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
ClC-2 is a broadly expressed Cl- channel of the CLC family of Cl- channels and transporters which is abundantly expressed in brain. Here it was proposed to participate in lowering the cytoplasmic Cl- concentration of neurons, a process that establishes an inhibitory response to the neurotransmitters GABA and glycine (Staley et al., 1996). Heterozygous mutations in CLCN2 (the gene encoding ClC-2) were recently reported in a few patients with three clinically distinct forms of epilepsy (Haug et al, 2003). However, the disruption of ClC-2 in mice (ClC-2 KO mouse) did not entail epilepsy (Bösl et al., 2001; Nehrke et al., 2002) but myelin vacuolation in fiber tracts of the central nervous system. We used a gene expression profiling of the ClC-2 KO mouse in brain to identify possible disease mechanism which cause the observed myelin phenotype. As these myelin vacuolation became apparent in the fiber tracts of ClC-2 KO cerebellum at P28 and increased with age, we analysed the cerebellum of ClC-2 KO mice at different postnatal ages, before (P14) and after (P35) the KO cerebellum has been affected by myelin vacuolation.
Publication Title
Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The Structural Maintenance of Chromosomes (SMC) complexes regulate the chromosome structures essential for proper genome regulation and cell viability. In mammals, the coordinated actions of the SMC complexes condensin I, condensin II and cohesin regulate dynamic chromosome structures throughout the cell cycle, but it is not clear how these complexes are positioned across the genome. We report here that condensin I, condensin II and cohesin occupy active euchromatic regions of the embryonic stem cell genome, but not heterochromatic regions. Like cohesin, we find that condensin II is deposited at active genes by the SMC loading factor Nipbl. The recruitment of Condensin II to active genes is dependent on their transcriptional activation. Subsequent transcriptional elongation by RNA polymerase II distributes condensin II across gene bodies. During mitosis, condensin I occupies the same set of active genes occupied by condensin II during interphase. Thus, SMC complexes are positioned in the genome by transcription-dependent processes, indicating that condensin-dependent condensation mechanisms are preferentially utilized in euchromatic regions. Overall design: RNA-seq in mES cells after known-down of Smc1, CapH2 or Smc2.
Publication Title
Multiple structural maintenance of chromosome complexes at transcriptional regulatory elements.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) is an oxidant responsive transcription factor known to induce phase 2 detoxifying and antioxidant genes to protect cells from oxidative stress. Cigarette smoke, with its large oxidant content, is a major stressor to the small airway epithelium, the cells of which are vulnerable to oxidant damage and consequent malignant transformation. In this study, we assessed the role of cigarette smoke in activation of Nrf2 in the human small airway epithelium in vivo. Fiberoptic bronchoscopy was used to sample a pure population of small airway epithelium in 38 healthy nonsmokers and 45 healthy smokers, and gene expression was assessed using Affymetrix HG-U133 Plus 2.0 microarrays. Compared to that of healthy nonsmokers, Nrf2 protein was significantly activated in the small airway epithelium of healthy normal smokers and localized in the nucleus (p<0.05). Of the human homologs of 201 known murine Nrf2-mediated genes, 13 highly smoking-responsive genes were identified (p<10-4, all comparisons smokers to nonsmokers). Using a Nrf2-index to quantify the extent of expression in the small airway epithelium of these 13 known Nrf2 genes, variability in the level of expression was observed among the 45 healthy smokers, but the variability was coordinately modulated among the 13 genes, an observation confirmed by TaqMan quantitative PCR. This variability in the coordinate level of expression of the 13 Nrf2-mediated genes was independent of the smoking history. Based on these observations, the Nrf2 index was used to evaluate whether other genes modulated by smoking in the small airway epithelium were also coordinately up- or down- modulated among the 45 healthy smokers. Two genes, pirin (PIR) and UDP glucuronosyltransferase 1 family polypeptide A4 (UGT1A4), not previously known to be modulated by Nrf2 were identified as being coordinately modulated among the 45 smokers. Both genes contain several functional antioxidant response elements in the promoter region. Using an electrophoretic mobility shift assay, these antioxidant response elements in the promoters of PIR and UGT1A4 responded in vitro to activated Nrf2. These observations are consistent with the concept that Nrf2 plays an important role in regulating cellular defenses against smoking in the highly vulnerable small airway epithelium cell population, and that there is variability among the population in the relative Nrf2 responsiveness to a similar oxidant burden.
Publication Title
Coordinate control of expression of Nrf2-modulated genes in the human small airway epithelium is highly responsive to cigarette smoking.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smokers weigh less and have less body fat than non-smokers, and increased body fat and weight gain are observed following smoking cessation. To assess a possible molecular mechanism underlying the inverse association between smoking and body weight, we hypothesized that smoking may induce the expression of a fat depleting gene in the airway epithelium, the cell population that takes the brunt of the stress of cigarette smoke. As a candidate gene we evaluated the expression of alpha2-zinc-glycoprotein1 (AZGP1), a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice and is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. To assess if smoking upregulates AZGP1 expression, microarray analysis with TaqMan confirmation was used to evaluate large airway epithelial samples obtained by fiberoptic bronchoscopy from 37 normal smokers and 55 normal nonsmokers. Both microarray and TaqMan analysis demonstrated that AZGP1 mRNA levels were higher in the large airway epithelium of normal smokers compared to normal nonsmokers (p<0.05, all comparisons). Western analysis of airway biopsies of smokers compared with nonsmokers demonstrated upregulation of AZGP1 at the protein level, and immunohistochemical analysis demonstrated upregulation of AZGP1 in secretory as well as neuroendocrine cells of smokers. In the context that AZGP1 is involved in lipolysis and fat loss, its overexpression in the airway epithelium of chronic smokers may represent one mechanism for the weight difference in smokers vs nonsmokers.
Publication Title
Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The methyl-cytosine binding protein 2 (MeCP2) is a reader of epigenetic DNA methylation marks and necessary and sufficient to reorganize 3D heterochromatin structure during cellular differentiation, e.g., myogenesis. In addition to global expression profile changes, myogenic differentiation is accompanied by 3D-heterochromatin reorganization that is dependent on MeCP2. MeCP2 is enriched at pericentric heterochromatin foci (chromocenters). During myogenesis, the total heterochromatin foci number per nucleus decreases while foci volumes and MeCP2 protein levels increase. Ectopic MeCP2 is able to mimic similar heterochromatin restructuring in the absence of differentiation.
Publication Title
Gene repositioning within the cell nucleus is not random and is determined by its genomic neighborhood.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
Publication Title
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Malignant Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. We depleted subunit combinations corresponding to either canonical (p50/RelA) or non-canonical (p52/RelB) dimers in the HL cell line L-1236 and performed Affymetrix microarray analysis. Knockdown of p52/RelB affected the expression of a significantly higher number of genes than the knockdown of p50/RelA. The two sets of target genes presented a partial overlap, however they also revealed specific genes that are involved in distinct aspects of tumor biology.
Publication Title
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Expression data from 22 human myotubes (7 healthy controls, 4 Dysferlinopathy (DYSF), 4 Caveolinopathy 3 (CAV3), 4 Facioscapulohumeral muscular dystrophy(FSHD) and 3 Four and a half LIM 1 protein deficiency FHL1).cDNA microarray data showed that cyclin A1 levels are specifically elevated in FSHD vs. other muscular disorders such as CAV3, DYSF, FHL1 and healthy control. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated levels of cyclin A1 also on the protein level.
Publication Title
Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1).
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Malignant cells of Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. Knockdown of a subunit combination corresponding to the non-canonical NF-B dimer (p52/RelB) in the HL cell line L-1236 caused up-regulation of a set of genes that are associated with hematopoietic and lymphoid organ development. As p52 can form homodimeric complexes, which can repress transcription either alone or in association with transcriptional repressors such as HDAC1, we knocked down p52 alone to analyze its role in gene repression in HL cells. We found that the single knockdown of p52 is indeed sufficient to up-regulate an interesting set of genes that may play a role in B-cell and/or HL development.
Publication Title
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Expression of germ cell nuclear factor (GCNF, Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.
Publication Title
Germ cell nuclear factor regulates gametogenesis in developing gonads.
Sample Metadata Fields
Specimen part
View Samples