Genes regulated by E47
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Tomokatsu Ikawa
PROVIDER: E-GEOD-4693 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In maturing T-lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell growth, lipid metabolism, stress response and lymphoid maturation. These include Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2 and Xbp1. We propose a regulatory network linking JAK/STAT mediated signaling, E47 and SOCS proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47 deficient T-lineage cells contributes to the development of lymphoid malignancy. We used the 1F9 cell line, originally isolated from E2A deficient thymomas. To identify E47 target genes, 1F9 cells were transduced with a retrovirus carrying an E47/estrogen receptor (E47ER) hybrid protein. Control cells were transduced with virus carrying the bHLH region but lacking the N-terminal transactivation domain. Both retroviral constructs also directed the expression of human CD25 (hCD25) to allow rapid isolation of transduced cells. One day post-infection, cells were incubated with 4-hydroxytamoxifen (4-OHT) for a period of six hours, to activate the E47ER fusion protein. hCD25 positive cells were purified using magnetic beads, RNA was isolated and used to generate probes for hybridization to murine oligonucleotide microarrays.
2010-07-01 | E-GEOD-4784 | biostudies-arrayexpress
Project description:To find the target genes regulated by E47 in hematopoietic progenitor cells Keywords: genetic modification
2006-04-22 | GSE4693 | GEO
Project description:In maturing T-lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell growth, lipid metabolism, stress response and lymphoid maturation. These include Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2 and Xbp1. We propose a regulatory network linking JAK/STAT mediated signaling, E47 and SOCS proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47 deficient T-lineage cells contributes to the development of lymphoid malignancy. Keywords: gene targets for E47
2006-05-09 | GSE4784 | GEO
Project description:We performed ChIP-Sequencing for E2A and GR in mouse livers and demonstrate that E47 co-occupies metabolic promoters and enhancers together with GR. Together with the corresponding RNA-Seq data, our results illustrate how GR and E47 synergize during the transcriptional activation of hepatic metabolism.
2018-11-30 | GSE111526 | GEO
Project description:The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity. The E2A-deficient Sézary cell line Seax was transiently transfected with the E2A-expression constructs E47myc (a myc-tagged E47 construct) or E47-forced dimer (a construct coding for two covalently linked E47 molecules), respectively. Every experiment was performed as two replicates accompanied by control transfections with a Mock plasmid.
2011-07-07 | E-GEOD-21730 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are widely prescribed effective drugs, but their clinical use is compromised by severe side effects including hyperglycemia, hyperlipidemia and obesity. They bind to the Glucocorticoid Receptor (GR), which acts as a ligand-gated transcription factor. The transcriptional activation of metabolic genes by GR is thought to underlie these undesired adverse effects. Using mouse genetics, ChIP-Seq, RNA-Seq and ChIP-MS, we found that the bHLH transcription factor E47 is required for the regulation of hepatic glucose and lipid metabolism by GR in vivo, and that loss of E47 prevents the development of hyperglycemia and hepatic steatosis in response to GCs. Here we show that E47 and GR co-occupy metabolic promoters and enhancers. E47 is needed for the efficient binding of GR to chromatin and for the adequate recruitment of coregulators such as Mediator. Taken together, our results illustrate how GR and E47 regulate hepatic metabolism, and how inhibition of E47 might provide an entry point for novel GC therapies with reduced side effect profiles. These ChIP-MS data sets show IPs for GR in both wildtype and E47 mutant mouse livers treated with the synthetic glucocorticoid Dexamethasone.
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Project description:E47 represses Foxp3 transcription, albeit indirectly through the activation of unknown negative regulatory of Foxp3 transcription. To identify target genes of E47 in regulatory T cells, we compared gene expression profiles of Treg cells overexpressing E47 compared to control-vector transduced cells.
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Project description:Genome-wide gene expression pattern of E47 KO versus WT HSCs from primary and secondary recipient mice were analysis using Agilent one-color micro-array analysis.
2011-01-22 | GSE26788 | GEO
Project description:We set out to identify genes that respond rapidly to overexpression of a Tcf15-E47 heterodimeric transcription factor in mouse embryonic stem cells. Dox inducible Tcf15-E47 mouse embryonic stem cells were exposed to dox for 0, 8, 12, 24h and samples collected in duplicate. Control parental cells were exposed to dox for 0 or 8 h and samples collected in duplicate. Total 12 samples.
2013-02-08 | E-GEOD-42539 | biostudies-arrayexpress
Project description:Analysis of induced E47 expression on PDA cells at the gene expression level.The hypothesis tested in the present study was that PDA cells can be reprogrammed to revert to their original quiescent acinar cell phenotype by stimulating a tamoxifen inducible form of E47 fused to a modified estrogen (E47-ER) receptor . Results provide important information on the remarkable ability of E47ER to trigger reactivation of the acinar cell differentiation program and cell cycle arrest in PDA cells.
2015-04-20 | GSE55999 | GEO