Binding of Runx1 and Runx3 in CD4+ T cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE100346 | GEO | 2020/03/02
REPOSITORIES: GEO
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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:The RUNX genes encode for transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here we show that Runx1;Runx3 double knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes like Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independent of CBFM-NM-2, suggesting non-transcriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes development of leukemias and other cancers. 6 mice were analyzed in this study. 3 Runx1;Runx3 double knockout cKit+Sca1+Lin- hematopoietic stem/progenitor cells were compared with their wild type littermate controls. RNA was isolated from 3 independent Runx1;Runx3 WT KSL samples, each pooled from 3 Runx1;Runx3 WT mice, and 3 independent Runx1;Runx3 DKO KSL samples, using the RNeasy Micro Kit (QIAgen). RNA integrity and quantity was assessed using the Agilent 2000 Bioanalyzer system. 3 M-NM-<g to 5 M-NM-<g RNA was processed using WT-Ovation Pico RNA Amplification System (NuGEN) paired with the WT-Ovation Exon Module and FL-Ovation cDNA Biotin Module (NuGEN). A detailed protocol in the userM-bM-^@M-^Ys guide kit was used without modification. cDNA were prepared for hybridization on GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix) according to the instructions in GeneChip Hybridization Wash and Stain Kit for ST arrays (Affymetrix). Microarray hybridization, scanning and preliminary MAS 5.0 normalizations were completed at the A*STAR Biopolis Shared Facilities (BSF).
2014-08-26 | E-GEOD-51107 | biostudies-arrayexpress
Project description:CD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells To identify Runx3 responsive genes CD4+ dendritic cells were sorted from freshly isolated macs enriched splenic DCs taken from 6 weeks old mice. Six samples from six mice were sorted and analyzed where in each littermates pair consisted of a control and Runx3 KO.
2014-06-22 | E-GEOD-48589 | biostudies-arrayexpress
Project description:ChIP-seq was conducted using FACS-isolated CD11chiMHCII+CD4+ splenic WT DC and anti-Runx3 antibodies (Ab). Two biological Runx3 IP repeats and two input controls from sorted CD4 DC
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Project description:The RUNX genes encode for transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here we show that Runx1;Runx3 double knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes like Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independent of CBFβ, suggesting non-transcriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes development of leukemias and other cancers.
2014-08-26 | GSE51107 | GEO
Project description:Runx1 and Runx3 cooperatively repress Pmp22 to drive neurofibromagenesis
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Project description:Pattens of tissue-residency differs between CD4+ and CD8+ memory T cells in evironmentally exposed organs. The lineage-controlling transcription factor Runx3, expressed in CD8+ T cells, is responsible for shaping a tissue-resident gene network in response to the cytokine TGF-b. While the lack of Runx3 by CD4+ T cells precludes these transcriptional changes, Runx3-overexpression in CD+ T cells enable phenotypical, transcriptional and functional changes to allow residency.
2022-05-24 | GSE182511 | GEO
Project description:Tissue-resident memory T (TRM) cells provide rapid and superior control of localized infections. The transcription factor Runx3 was recently identified as a master regulator of CD8+ T cell tissue residency. However, Runx3 also drives CD8+ T cell lineage commitment and is repressed in CD4+ T cells, raising the possibility that this transcription factor defines a form of tissue residency unique to the CD8+ T cell subset. Here, we show that as a direct consequence of Runx3-deficiency, CD4+ TRM cells in epithelia lack the TGFb-responsive transcriptional network that underpins CD8+ TRM cell residency. Ectopic Runx3 expression in CD4+ T cells rescued this transcriptional program to promote prolonged survival, decreased tissue egress and a microanatomical redistribution towards epithelial layers that combined, resulted in superior local immune protection. Our results thus reveal a mechanistic discordance between CD4+ and CD8+ TRM cell formation in barrier tissues that is controlled by Runx3. Consequently, CD4+ TRM cells are unable to adopt a type of tissue residency that is intrinsically accessible to the CD8+ TRM cell subset.
2022-05-24 | GSE198611 | GEO
Project description:ChIP-seq was conducted using FACS-isolated CD11chiMHCII+CD4+ splenic WT DC and anti-Runx3 antibodies (Ab).
2014-06-22 | GSE48588 | GEO
Project description:Runx3 regulated genes in splenic CD4+ dendritic cells
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