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GSE11586
Mus musculus
5 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Processing of Immunoglobulin heavy chain (IgH) mRNA is a paradigm for competition between splicing and polyadenylation. In plasma cells pre-mRNA is polyadenylated mainly at the promoter-proximal secretory site while B-cells utilize a cryptic 5 splice site in the last secretory-specific exon; these are mutually exclusive events for all IgH pre-mRNAs. Transcription elongation factor ELL2, more abundant in plasma cells relative to B-cells, was down-modulated by overexpression of heterogenous ribonucleoprotein F, a condition which reduced production of secretory IgH mRNA. Transfection of B-cells with ELL2 and the IgH reporter showed an accelerated use of the secretory poly(A) site, positioned in competition with the splice to M1; a small interfering RNA to ELL2 reduced expression of IgH secretory mRNA. Co-transcription factors ELL1 and PC4 were ineffective at driving secretory-poly(A) site use. ELL2 had little effect on poly(A) site choice with reporters containing tandem-linked poly(A) sites. Shorter forms of ELL2 protein result from both internal initiation at M186 and protein processing. An alternative splicing reporter driven by IgH or non-Ig promoters revealed that ELL2 and its M186 initiated form were able to accelerate exon skipping. Therefore, ELL2 influences IgH pre-mRNA processing through facilitating skipping of the alternative splice to the membrane form.
Publication Title
Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Clone (Whirly) of human BJhTERT (human foreskin cell line) cells exposed to PC3 mRFP cells
Publication Title
Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Different fibroblast cells (eight in total) with different inhibitory capacity were analyzed and compared for their gene expression profile by whole genome microarray.
Publication Title
Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 5 Downloadable Samples
Description
The heart adapts to increased workload through hypertrophic growth of cardiomyocytes. Although beneficial when induced physiologically by exercise, pathological cues including hypertension cause reexpression of fetal genes and dysfunctional hypertrophy, with lasting consequences for cardiac health. We hypothesised that these differences are driven by changes in chromatin-encoded cellular memory. We generated genome-wide maps of transcription and of two stable epigenetic marks, H3K9me2 and H3K27me3, specifically in hypertrophied cardiomyocytes, by selectively flow-sorting their nuclei. This demonstrated a pervasive loss of euchromatic H3K9me2 specifically upon pathological but not physiological hypertrophy, derepressing genes associated with pathological hypertrophy. Levels of the H3K9 methyltransferases, G9a and GLP, were correspondingly reduced. Importantly, pharmacological or genetic inactivation of these enzymes was sufficient to induce pathological hypertrophy and the dedifferentiation associated with it. These findings suggest novel therapeutic opportunities by defining an epigenetic state of cardiomyocytes, acquired during maturation, which is required for maintaining cardiac health. Overall design: Examination of 2 different histone modifications and RNA expression in cardiomyocyte nuclei flow-sorted from hypertrophic rat hearts
Publication Title
The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Gene expression analysis of BJhTERT RhoA-KO and PC3 mRFP was performed before and after six days confrontation in co-cultivation. Analyses of original and control fibroblasts was also performed.
Publication Title
RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BCOR regulates myeloid cell proliferation and differentiation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.
Publication Title
BCOR regulates myeloid cell proliferation and differentiation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The hlh-30 gene encodes a C. elegans basic-helix-loop-helix (bHLH) transcription factor; We compared RNA from wild type worms and worms mutant for the hlh-30 gene to identify putative target genes of the HLH-30 transcription factor.
Publication Title
A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.
Publication Title
Circadian clock cryptochrome proteins regulate autoimmunity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples