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GSE31092
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.
Publication Title
Role of ZBP-89 in human globin gene regulation and erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Engagement of the ICOS receptor represents a key event in a process that culminates in Bcl6 expression and acquisition of the TFH and TFR phenotype. To better understand the essentials of ICOS-mediated signaling pathway, we profiled the changes in gene expression elicited after co-ligation of ICOS and CD3 compared with CD3 ligation alone.
Publication Title
A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A major limitation in the cancer treatment is the ability of cancer cells to become resistant to chemotherapeutic drugs, by multidrug establishment. Here, we evaluate the possibility to utilize MC70, either as ABC transporters inhibitor or as anticancer agent, in monotherapy or in combination with doxorubicin for cancer treatment. The study was carried out in MCF7/ADR and Caco-2, breast and colon cancer cells, respectively. Cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectively. Cell cycle perturbation and cellular targets modulation were analyzed by flowcytometry and western blotting, respectively. MC70 was analyzed for its interaction with ABC transporters, MDR-1, BCRP and MRP-1, and for its anticancer activity. In MCF7/ADR, MC70 slight inhibited cell proliferation and strongly enhanced doxorubicin effectiveness; conversely in Caco-2, it inhibited cell growth without affecting doxorubicin efficacy. In addition, it induced apoptosis, canceled in favor of necrosis when it was given in combination with high doses of the anthracycline. Moreover, MC70 inhibited cell migration probably through its residual activity as sigma-1 ligand. Among the hypothesized molecular and cellular mechanisms responsible for all these effects, modulations of cell cycle, of pAkt and of the three MAPKs phosphorylation were evidenced while activity at transcription level was excluded. MC70 can be considered as a potential new anticancer agent with the capability to enhance doxorubicin effectiveness and an interesting role in the treatment of chemotherapy resistant tumors.
Publication Title
MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Identification of genes regulated by GATA-1 independent of the cofactor FOG-1.
Publication Title
Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.
Publication Title
Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.
Publication Title
Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
We report differences in gene expression between WT and Bmi1 KO pro-B cells. Overall design: RNA profiles from WT and Bmi1 KO pro-B cells were generated in duplicate.
Publication Title
Impaired Expression of Rearranged Immunoglobulin Genes and Premature p53 Activation Block B Cell Development in BMI1 Null Mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional approaches. In this study, we report that the histone deacetylase associated SIN3B protein is required for activated KRAS-induced senescence in vivo using a mouse model of pancreatic cancer.
Publication Title
Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 79 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an etiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1/FOX1, and a module enriched for immune genes and glial markers. Using high-throughput RNA-sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in ASD brain. Moreover, using a published autism GWAS dataset, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic etiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
Publication Title
Transcriptomic analysis of autistic brain reveals convergent molecular pathology.
Sample Metadata Fields
Disease
View Samples- Mus musculus, Homo sapiens
- 22 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples