Transcription profiling of mouse embryos at 8.5 and 12 days to study the effect of knocking out RUNX1 (a.k.a. AML1) gene
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Ken Simpson
PROVIDER: E-GEOD-2592 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Series of samples studying effect of knocking out RUNX1 (a.k.a. AML1) in mouse embryos at 8.5 and 12 days. Wildtype and knockout animals at the two time points were generated and all conditions done in duplicate. Keywords: other
2005-12-02 | GSE2592 | GEO
Project description:Human histone deacetylase 3 (HDAC3) plays an important role in gene transcription in diseased human cells, such as leukemia. The t(8;21) chromosomal translocation is one of the most commonly observed genetic abnormalities associated with acute myeloid leukemia. This translocation generates the AML1-ETO fusion protein between the wild-type RUNX1 transcription factor and wild-type ETO transcriptional corepressor. To better understand the role of HDAC3 in t(8;21) leukemogenesis, the human HDAC3-containing complexes were isolated from stably-transfected HeLa cells by using anti-FLAG immunoprecipitation. The resulting complexes were resolved in SDS-PAGE. The components of the complexes were identified using LC-MS/MS. We report here that the human RUNX1 transcription is a component of the HDAC3 complexes. We demonstrate that HDAC3 and RUNX1 collaboratively repress AML1-ETO-mediated transcription. These results reveal new insight into how AML1-ETO, RUNX1, and HDAC3 crosstalk to deregulate gene transcription in t(8;21) leukemia cells.
2020-02-17 | PXD017230 | Pride
Project description:The t(8;21) acute myeloid leukemia associated oncoprotein AML1-ETO is a transcription factor that aberrantly regulates the pathways that lead to myeloid differentiation. Here, we set out to investigate the effects of AML1-ETO on gene expression and the epigenome in patient blast cells. We identify two modules, one in which AML1-ETO binds promoter regions of active genes and one represented by non-promoter binding to accessible, yet inactive chromatin regions. Using genome-wide binding analysis and mass spectrometry interaction studies we identify ERG, FLI1, TAL1 and RUNX1 as common binding factors of all AML1-ETO occupied genomic regions, while LYL1 and LMO2 show preferential binding in the context of non promoter regions. Epigenetically, reduced histone acetylation levels at non-promoter regions seems HDAC dependent, as treatment with an HDACi increases acetylation and induces cell death. Both AML1-ETO modules are represented in most aberrantly regulated pathways, including many signaling pathways, self-renewal and apoptosis. For the latter, the expression of the wild type transcription factors RUNX1 and ERG is required, as alterations in expression are associated with the onset of an apoptosis program. Interestingly, upon RUNX1 or ERG knockdown this onset seems to be dependent on increased AML1-ETO expression as combinatorial knockdown of RUNX1/AML1-ETO or ERG/AML1-ETO results in rescue from apoptosis. Together our results show that the balanced interplay of the epigenetic environment and transcription factors retains an anti apoptotic phenotype in t(8;21) AML cells.
2016-11-15 | GSE76464 | GEO
Project description:TEL-AML1 (ETV6-RUNX1) in B-cells and leukemia
| PRJNA218611 | ENA
Project description:To clarify how Foxp3 regulates its target genes, we performed co-immunoprecipitation experiments and found that Foxp3 physically bound to AML1/Runx1 (Ono, M. et al, Nature, 2007). In this series of study, we compared gene regulations by AML1, wild type Foxp3, and a Foxp3 mutant with defective binding to AML1. Keywords: Retroviral gene-transduction into primary CD4+ T cells
2007-08-01 | GSE6939 | GEO
Project description:Cancer cells maintain a sensitive balance between growth-promoting oncogenes and apoptosis inhibitors. We show that WT RUNX1 is required for survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 AML cell lines. The malignant AML phenotype is sustained by a delicate AML1-ETO/RUNX1 balance that involves competition for common DNA binding sites regulating a subset of AML1-ETO/RUNX1 targets. Genome expression was profiled after performing knockdown of RUNX1 and AML1-ETO in Kasumi-1 cells using specific siRNA-oligo nucleotides, and analyzed using Affymetrix Gene 1.0 ST arrays.
2013-08-18 | E-GEOD-45743 | biostudies-arrayexpress
Project description:Cancer cells maintain a sensitive balance between growth-promoting oncogenes and apoptosis inhibitors. We show that WT RUNX1 is required for survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 AML cell lines. The malignant AML phenotype is sustained by a delicate AML1-ETO/RUNX1 balance that involves competition for common DNA binding sites regulating a subset of AML1-ETO/RUNX1 targets. Genomewide sequencing data is included herein: Transcription factors RUNX1 c-terminus and n-terminus which is shared with AML1-ETO were profiled independently), AML1-ETO and AP4 were profiled using ChIP-Seq in Kasumi-1 cells, as well as control ChIP-Seq experiments of non immune serum. Two replicates were performed for each transcription factor profiling and control experiment.
2013-08-18 | E-GEOD-45738 | biostudies-arrayexpress
Project description:Mononuclear cells were isolated from umbilical cord blood (UCB) using Lymphoprep sucrose-gradient centrifugation (1.077 g/ml, Nycomed Pharma, Oslo, Norway). Immunomagnetic cell separation, using magnetic beads coated with CD34 antibodies (Miltenyi Biotec, Gladbach, Germany), was performed to isolate CD34-positive hematopoietic progenitor cells (CB-CD34+ cells). To generate retrovirus, bicistronic retroviral DNA constructs were used expressing the ETV6-RUNX1 or AML1-ETO fusion gene and enhanced Green Fluorescent Protein (eGFP). As a control, a construct expressing only eGFP was used. Both vectors consisted of a pMSCV promoter region, an internal ribosomal entry site and an ampicillin resistance cassette. HEK293T cells were co-transfected with these constructs and second-generation retroviral packaging vectors using XtremeGENE 9 tranfection reagents (Roche, Basel, Switzerland). Viral particles were collected in IMDM 48 hours after transfection. CD34+ haematopoietic progenitors, pre-cultured overnight as described above, upon which cells were divided in two fractions. One fraction was transduced with ETV6-RUNX1-IRES-eGFP or AML1-ETO-IRES-eGFP, while the other fraction was transduced with control EV-IRES-eGFP. Transductions were performed with fresh retrovirus in retronectin (Takara, Otsu, Japan) coated wells. After sorting, DAPI- CD34+ GFP+ CB-CD34+ cells were lysed and RNA was extracted using Nucleospin RNA XS extraction columns according to manufacturer’s protocol (Macherey-Nagel, Düren, Germany). Quality of RNA was determined by on-chip-electrophoresis using a RNA Pico Chip according to manufacturer’s protocol (Agilent Technologies, Santa Clara, CA, USA). RNA Integrity scores (RIN) were higher than 8 for all samples. RNA was subsequently linearly amplified using the Nugen WT-Amplification™ pico system (Nugen, San Carlos, CA, USA). This system is based on RNA-dependent DNA polymerase activity and was previously reported to be most suitable for amplification and gene expression of picograms of input RNA.
2019-01-01 | E-MTAB-3466 | biostudies-arrayexpress
Project description:Cancer cells maintain a sensitive balance between growth-promoting oncogenes and apoptosis inhibitors. We show that WT RUNX1 is required for survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 AML cell lines. The malignant AML phenotype is sustained by a delicate AML1-ETO/RUNX1 balance that involves competition for common DNA binding sites regulating a subset of AML1-ETO/RUNX1 targets.
2013-08-18 | GSE45743 | GEO
Project description:Cancer cells maintain a sensitive balance between growth-promoting oncogenes and apoptosis inhibitors. We show that WT RUNX1 is required for survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 AML cell lines. The malignant AML phenotype is sustained by a delicate AML1-ETO/RUNX1 balance that involves competition for common DNA binding sites regulating a subset of AML1-ETO/RUNX1 targets.
2013-08-18 | GSE45738 | GEO