E-cadherin and EMT regulation by E47 transcription represor
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris Homo sapiens
PROVIDER: GSE9147 | GEO | 2008/12/21
SECONDARY ACCESSION(S): PRJNA102693
REPOSITORIES: GEO
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Project description:Expression profile analysis in MDCK-E47 cells in comparisom with MDCK CMV control cells Keywords: Genetic Modification (overexpression of E-cadherin repressors) The Oncochip microarray platform v1.1 contains 9,726 clones corresponding to 6,386 different genes, and it includes 2,489 duplicate clones. Duplicate samples (different extrations of RNA) were labeled with dUTP-Cy5 and hybridized against dUTP-Cy3-MDCK control cells. In addittion, one RNA extraction was labelled with dUTP-Cy3 and was hybridized againts dUTP-Cy5- CMV control cells
2010-06-24 | E-GEOD-9147 | biostudies-arrayexpress
Project description:Loss of expression of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration in the developing embryo and during tumour invasion. Transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation in most carcinomas. Recently, we have identified the class I HLH transcriptional regulator E2-2 (ITF2), in a yeast one hybrid screen designed to identify transcriptional repressors interacting with the E-pal element of the murine E-cadherin promoter. The E2-2 gene codifies two isoforms that differ in their N-terminal regions but their specific functions remain unknown. In the present work we show that both E2-2A and E2-2B induce a complete EMT, in MDCK cells, with loss of E-cadherin expression, gain of mesenchymal markers and acquisition of motile and invasive properties. Although both isoforms repress E-cadherin promoter in MDCK cells, only the E2-2B isoform does it in other epithelial cell lines. Notably, we found that E2-2B is upregulated at the mRNA level in MDCK cells after treatment with TGF-ï¢1, a key regulator of EMT. Upregulation of E2-2A/B factors was confirmed in MDCK cells overexpressing other EMT inducers, Snai1, Snai2 or E47. Interestingly, gene profiling studies indicate that bHLH E2-2 factors induce similar, yet distinct, genetic programs from those induced by bHLH E47 in MDCK cells. These results, together with the expression pattern observed in early mouse embryos, support a new role for E2-2A/B in E-cadherin regulation and EMT, and suggest an interesting interplay between bHLH factors and other E-cadherin repressors. Keywords: Genetic Modification (overexpression of E-cadherin repressors) The Oncochip microarray platform v2.0 contains 13,824 clones printed by duplicate corresponding to 9,300 different genes. Each of the MDCK transfectants (E22A, E22B) were labeled with dUTP-Cy5 and hybridized against the dUTP-Cy3-labeled MDCK-CMV controls. One additional hybridizations using reciprocal fluorochrome labeling were performed (dye-swap) in each clone. Thus, a total of two hybridizations were performed for each condition.
2010-06-24 | E-GEOD-9145 | biostudies-arrayexpress
Project description:Gene expression profiling of MDCK epithelial cells expressing different repressors (MDCK-Snail, MDCK-Slug and MDCK-E47 cells) versus control MDCK cells. Keywords: Genetic Modification (overexpression of E-cadherin repressors)
2006-11-02 | GSE4151 | GEO
Project description:Loss of expression of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration in the developing embryo and during tumour invasion. Transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation in most carcinomas. Recently, we have identified the class I HLH transcriptional regulator E2-2 (ITF2), in a yeast one hybrid screen designed to identify transcriptional repressors interacting with the E-pal element of the murine E-cadherin promoter. The E2-2 gene codifies two isoforms that differ in their N-terminal regions but their specific functions remain unknown. In the present work we show that both E2-2A and E2-2B induce a complete EMT, in MDCK cells, with loss of E-cadherin expression, gain of mesenchymal markers and acquisition of motile and invasive properties. Although both isoforms repress E-cadherin promoter in MDCK cells, only the E2-2B isoform does it in other epithelial cell lines. Notably, we found that E2-2B is upregulated at the mRNA level in MDCK cells after treatment with TGF-beta1, a key regulator of EMT. Upregulation of E2-2A/B factors was confirmed in MDCK cells overexpressing other EMT inducers, Snai1, Snai2 or E47. Interestingly, gene profiling studies indicate that bHLH E2-2 factors induce similar, yet distinct, genetic programs from those induced by bHLH E47 in MDCK cells. These results, together with the expression pattern observed in early mouse embryos, support a new role for E2-2A/B in E-cadherin regulation and EMT, and suggest an interesting interplay between bHLH factors and other E-cadherin repressors.
2008-12-21 | GSE9145 | GEO
Project description:Gene expression profiling of MDCK epithelial cells expressing different repressors (MDCK-Snail, MDCK-Slug and MDCK-E47 cells) versus control MDCK cells. The Oncochip microarray platform v1.1 contains 9,726 clones corresponding to 6,386 different genes, and it includes 2,489 duplicate clones. Duplicate samples from each of the MDCK transfectants (E47, SNAIL, SLUG) were labeled with dUTP-Cy5 and hybridized against the dUTP-Cy3-labeled MDCK-CMV controls. Two additional hybridizations using reciprocal fluorochrome labeling were performed (dye-swap). Thus, a total of four hybridizations were performed for each condition.
2010-07-01 | E-GEOD-4151 | 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:Cell plasticity is emerging as a key regulator of tumor progression and metastasis. During carcinoma dissemination epithelial cells undergo epithelial to mesenchymal transition (EMT) processes characterized by the acquisition of migratory/invasive properties, while the reverse, mesenchymal to epithelial transition (MET) process, is also essential for metastasis outgrowth. Different transcription factors, called EMT-TFs, including Snail, bHLH and Zeb families are drivers of the EMT branch of epithelial plasticity, and can be post-transcriptionally downregulated by several miRNAs, as the miR-200 family. The specific or redundant role of different EMT-TFs and their functional interrelations are not fully understood. To study the interplay between different EMT-TFs, comprehensive gain and loss-of-function studies of Snail1, Snail2 and/or Zeb1 factors were performed in the prototypical MDCK cell model system. We here describe that Snail1 and Zeb1 are mutually required for EMT induction while continuous Snail1 and Snail2 expression, but not Zeb1, is needed for maintenance of the mesenchymal phenotype in MDCK cells. In this model system, EMT is coordinated by Snail1 and Zeb1 through transcriptional and epigenetic downregulation of the miR-200 family. Interestingly, Snail1 is involved in epigenetic CpG DNA methylation of the miR-200 loci, essential to maintain the mesenchymal phenotype. The present results thus define a novel functional interplay between Snail and Zeb EMT-TFs in miR200f regulation providing a molecular link to their previous involvement in the generation of EMT process in vivo. Expression analysis of MDCK over-expression EMT-TF Analysis of 7 overexpression MDCK cells each of them using biological rpelicates (MDCK-E47, Snail2, Snail1, Twist1, Tiwst2, Zeb1, Zeb2)
2014-09-09 | E-GEOD-61217 | biostudies-arrayexpress
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: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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