Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA205236 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identify the target genes of Runx1/Cbfb in MLL fusion leukemia, we performed microarray analysis using control and Runx1/Cbfb-deleted MLL-AF9 cells.
2013-06-30 | GSE47350 | GEO
Project description:To identify the target genes of Runx1/Cbfb in MLL fusion leukemia, we performed microarray analysis using control and Runx1/Cbfb-deleted MLL-AF9 cells. c-Kit(+) bone marrow cells derived from Runx1/Cbfb double floxed mice were transduced with MLL-AF9 and CreERT2 (coexpressing Puromycin). After several rounds of replating with Puromycin, EtOH (control) or 4OHT was added to induce gene deletion. Two independent experiments with 2 independent clones were performed, and gene-expression was compared using the 4 sets of samples 24 hours after 4OHT addition.
2013-06-30 | E-GEOD-47350 | biostudies-arrayexpress
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and DNMT3B encode the two methyltransferases that are primarily responsible for the de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are rarely found in AML patients with translocations that create oncogenic fusion genes (e.g. PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X). To begin to define the reasons why these mutations do not occur together, we used retroviral vectors to express PML-RARA, RUNX1-RUNX1T1, and MLL-AF9 in the bone marrow cells of wild type (WT) or Dnmt3a deficient mice; we also examined the hematopoietic phenotypes of Ctsg-PML-RARA animals (which express PML-RARA in early hematopoietic progenitors and myeloid precursors) with and without Dnmt3a. We demonstrated that the methyltransferase activity of Dnmt3a (but not Dnmt3b) is required for aberrant self-renewal ex vivo that is driven by PML-RARA (but not RUNX1-RUNX1T1 or MLL-AF9); furthermore, the PML-RARA-driven competitive transplantation advantage and leukemia generation both required Dnmt3a. Together, these findings demonstrate that PML-RARA is specifically dependent on Dnmt3a to initiate APL in mice, and may explain why loss-of-function DNMT3A mutations are not found in patients with acute promyelocytic leukemia.
2015-10-01 | GSE68844 | GEO
Project description:In MLL-rearranged (MLLr) leukemias the N terminal part of the MLL gene can be fused to over 60 different partner genes. Here, we investigate the genome wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and their epigenetic signatures in order to define a core set of MLLr targets. We uncover both common as well as specific MLL-AF9 and MLL-AF4 target genes, which are all marked by H3K79me2, H3K27ac, and H3K4me3. Apart from promoter binding, we also identify MLL-AF9 and MLL-AF4 binding at specific subsets of non overlapping active distal regulatory elements. Despite this differential enhancer binding MLL-AF9 and MLL-AF4 still share a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34+ and monocyte specific genes. Comparing these datasets revealed several zinc finger transcription factors as potential MLL-AF9 co-regulators. Together these results suggest that MLL-fusions collaborate with specific subsets of TFs to aberrantly regulate the RUNX1 gene program in 11q23 AMLs.
2017-01-24 | GSE79899 | GEO
Project description:Gene expression profiles of Cbfb-deficient and control Treg cells were compared. Abstract: Naturally arising regulatory T (Treg) cells express the transcription factor FoxP3, which critically controls the development and function of Treg cells. FoxP3 interacts with another transcription factor Runx1 (also known as AML1). Here we showed that Treg cell-specific deficiency of Cbfβ, a cofactor for all Runx proteins, or that of Runx1, but not Runx3, induced lymphoproliferation, autoimmune disease, and hyper-production of IgE. Cbfb-deleted Treg cells exhibited impaired suppressive function in vitro and in vivo, with altered gene expression profiles including attenuated expression of FoxP3 and high expression of interleukin-4. The Runx complex bound to more than 3000 gene loci in Treg cells, including the Foxp3 regulatory regions and the Il4 silencer. In addition, knockdown of RUNX1 showed that RUNX1 is required for the optimal regulation of FoxP3 expression in human T cells. Taken together, our results indicate that the Runx1-Cbfβ heterodimer is indispensable for in vivo Treg cell function, in particular, suppressive activity and optimal expression of FoxP3. Experiment Overall Design: CD4+CD25hi cells, most of which were Foxp3+ Treg cells, were isolated from Cbfb-flox/flox: Foxp3-ires-Cre (n = 3) and control Cbfb-flox/wt: Foxp3-ires-Cre (n = 3) mice. Total RNA was extracted from those purified Cbfb-deficient or control Treg cells.
2009-09-25 | E-GEOD-18148 | biostudies-arrayexpress
Project description:Cbfb/Runx1-repression independent blockage of differentiation and accumulation of Csf2rb expressing cells by Cbfb-MYH11
| PRJNA120677 | ENA
Project description:MLL-AF9 transforms committted progenitors to leukemia stem cells
| PRJNA94653 | ENA