Similar Datasets
Project description:Identification of RUNX1 and ETV6-RUNX1 binding sites
2022-04-10 | E-MTAB-10312 | biostudies-arrayexpress
Project description:RUNX1 and ETV6-RUNX1 possess the same DNA-binding runt domain and are therefore expected to bind to canonical RUNX motifs. As the ETV6-RUNX1 fusion arises in the context of native RUNX1 expression, and since RUNX1 is retained or amplified in B-ALL, the two proteins are likely to compete for the same target sites. To assess this, we performed RUNX1 ChIP-seq in the presence of exogenous ETV6-RUNX1 (or non DNA binding ETV6-RUNX1-R139G) and the reciprocal experiment: ETV6-RUNX1 ChIP (using a V5 tag) in the presence of exogenous RUNX1 or vector control.
2022-10-31 | E-MTAB-12209 | biostudies-arrayexpress
Project description:The overall goal of this study is to identify the genomic binding of RUNX1 in MCF10A cells. We used ChIPseq (chromatin immunoprecipitation assay followed by deep sequencing) to identify the binding sites of RUNX1 in MCF10A cells. We performed ChIPseq of RUNX1 using parental MCF10A cells and did not identify high confident binding sites. To overcome this hurdle, we first generated a RUNX1 deleted MCF10A cell line using CRISPR-Cas9. We then transduced this RUNX1 KO MCF10A cells with lentiviruses that inducibly expresses RUNX1. After treating RUNX1 inducible MCF10A cells with 1 ug/ml doxycycline for 24 hours, we performed ChIPseq of RUNX1.
2019-04-18 | GSE129314 | GEO
Project description:ETV6-RUNX1 is a first-hit mutation in childhood B cell precursor acute lymphoblastic leukaemia. ETV6-RUNX1 is a fusion protein which inherits the DNA-binding runt domain from RUNX1. Here we performed chromatin precipitation for native RUNX1 and ETV6-RUNX1 using RUNX1 antibodies and specifically for the ETV6-RUNX1 fusion using a V5-tag pull down.
2022-10-31 | E-MTAB-12208 | biostudies-arrayexpress
Project description:Aneuploidy and structural aberrations affecting chromosome 21 (Hsa21) are the most frequent in cytogentic events in acute myeloid leukemia. However, it remains unclear why leukemic blasts select for amplifications of Hsa21 or parts of it and why children with Down syndrome (i.e. trisomy 21) are at a high risk of developing leukemia. Here, we propose that disequilibrium of the RUNX1 isoforms and resultant RUNX1A dominance are key to trisomy 21-associated leukemogenesis. Using a Hsa21-focussed CRISPR-Cas9 screen, we uncovered a strong and specific RUNX1 dependency in myeloid leukemia associated with Down syndrome (ML-DS). High levels of RUNX1A – as seen in ML-DS – synergized with the pathognomonic Gata1s mutation in ML-DS pathogenesis, an effect that was reversed upon restoration of the normal RUNX1A:RUNX1C equilibrium. Mechanistically, RUNX1A displaces RUNX1C from its endogenous binding sites and recruits the MYC cofactor MAX to induce oncogenic programs and perturb normal differentiation. This presents a therapeutic vulnerability that can be exploited by interfering with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, and paves the way for developing specific and targeted therapies for ML-DS as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.
2023-05-10 | PXD030616 | Pride
Project description:The T-cell leukemia homeobox 1 (TLX1, HOX11) transcription factor is critically involved in the multistep pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanisms by which these T-cell specific oncogenes cooperate during transformation remain to be established. Here, we used an integrative genomics approach to show that the oncogenic properties of TLX1 are mediated by genome-wide interference with the ETS1 and RUNX1 transcription factors. Partial disruption of ETS1 and RUNX1 activity by ectopic TLX1 expression in immature thymocytes drives repression of T-cell specific super-enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 signaling. These phenomena coordinately trigger a TLX1 driven pre-leukemic phenotype in human thymic precursor cells, which corresponds with the in vivo thymic regression observed in murine TLX1 tumor models, and creates a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multistep pathogenesis of TLX1 driven human leukemia. Gene expression was measured in the ALL-SIL T-ALL cell line after electroporation with scrambled siRNA and 2 independent RUNX1 targetings siRNAs. Cells were collected 24h after treatment. This was performed for 3 replicates.
2015-08-05 | E-GEOD-62140 | 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:The t(12;21) chromosomal translocation, targeting the gene encoding the RUNX1 transcription factor, is observed in 25% of pediatric acute lymphoblastic leukemia (ALL) and is an initiating event in the disease. To elucidate the mechanism by which RUNX1 disruption initiates leukemogenesis, we investigated its normal role in murine B-cell development. Gene expression analysis and genome-wide Runx1-occupancy studies support the hypothesis that Runx1 reinforces the transcription factor network in B-cell progenitors governing early B-cell survival and development . ChIP-seq experiments were performed in the proB-cell line BMiFLT3(15-3), stably transduced with the transcription factor Runx1, to identify Runx1-bound sites in early B-cell progenitors.
2013-05-27 | E-GEOD-45377 | 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 | GSE45738 | GEO
Project description:RUNX1 Chip-Seq of human early thymopoieisis
| PRJNA566133 | ENA