Gfi1 knockout in Raw264.7 macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE152868 | GEO | 2020/06/20
REPOSITORIES: GEO
Similar Datasets
Project description:Gfi1 knockout in Raw264.7 macrophages
| PRJNA640669 | ENA
Project description:This study investigates the proteomic alterations in bone marrow neutrophils isolated from 5-8 week old Gfi1+/-, Gfi1K403R/-, Gfi1R412X/-, and Gfi1R412X/R412X mice using the SWATH-MS technique. This dataset consists of 26 raw MS files, comprising 13 DDA (for spectral library generation)and 13 DIA (for SWATH) runs on a TripleTOF 5600 plus (SCIEX). Our findings revealed significant changes in the expression of neutrophil granule proteins and NADPH-oxidase complex components in Gfi1-mutant neutrophils.
2020-04-07 | PXD010943 | Pride
Project description:Abarrent transcriptional regulation is one of hallmarks of leukemia. GFI1 is a transcriptional regulator with context-dependent roles in hematopoiesis and leukemogenesis. Reduced or loss of GFI1 expression has been reported in myeloid malignancies, while high GFI1 expression has been observed in AML1-ETO-positive acute myeloid leukemia (AML) and acute lymphoid leukemia, but without clear roles defined for GFI1 in APL pathogenesis. We here performed ChIP-seq analysis using antibodies against GFI1 and identified genome-wide binding site of GFI1 in NB4 cells.
2020-08-26 | GSE154269 | GEO
Project description:Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we made use of mass spectrometry approaches. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is colocated on chromatin genome-wide with GFI1 and LSD1; the strongest HMG20B binding colocates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukaemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing the interaction on chromatin of LSD1 with GFI1. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukaemia cell differentiation block.
2023-03-11 | PXD030581 | Pride
Project description:The zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity. Experiment Overall Design: Splenic B220+CD19+ CD138- B cells of 4 week old Gfi1+/+ and Gfi1-/- mice were isolated and RNA was extracted from one sample per group and microarray analysis was performed.
2008-10-25 | E-GEOD-12545 | biostudies-arrayexpress
Project description:GFI1 is a transcriptional repressor protein that plays an essential role in HSCs development, lymphoid and myeloid differentiation and Acute Myeloid Leukaemic (AML) pathogenesis. Low expression levels of GFI1 is associated with a poor prognosis in AML development. In addition, a single nucleotide polymorphism (SNP) variant of GFI1 results in the generation of GFI1 protein with asparagine (N) instead of serine (S) at the 36th amino acid position, known as GFI136N. Expression of the GFI1-36N allele leads as well to poor prognosis and promotes AML development. In this study, we demonstrated with the help of RNAseq transcriptomic analysis that the presence of GFI1-36N is associated with increased frequency of chromosomal aberrations and mutational burden in murine and human AML cells. In particular, GFI1-36N modulates DNA repair pathways, O6-methylguanine-DNA-methyltransferase (MGMT)-mediated repair and homologous recombination repair (HR). Mechanistically, GFI1-36N exhibits impaired binding to Ndrg1 promoter element compared to GFI1-36S (wild type), causing decreased NDRG1 levels, consequently leading to suppression of MGMT expression, imprinted at the transcriptome and proteome, thus leaving the AML cells vulnerable to DNA damaging agents. Furthermore, we showed that a low expression level of GFI1 in leukemic cells is associated with high OXPHOS and enhanced glutamine metabolism. However, we hypothesise that the observed metabolic phenotype is mediated through FOXO1 protein. RNAseq transcriptomic analysis revealed higher Foxo1 mRNA expression levels with lower GFI1 expression, providing the first hint of Foxo1 as a potential target gene of GFI1 protein. The mRNA and protein levels of high Foxo1 with reduced GFI1 expression was confirmed by RT-PCR and western blot, respectively. In addition, CHIPseq and ATACseq analysis further proved that Foxo1 is a potential target gene of GFI1. In summary, we show that GFI1 plays a role during DNA repair and metabolism and thus provides critical insights into a novel therapeutic option for AML patients carrying the GFI1-36N variant or having a low expression level of GFI1.
2023-12-01 | GSE195955 | GEO
Project description:The goal of this study is to compare transcriptome-wide Nm-seq on the poly A+ RNA of wild-type Raw264.7 macrophages to transcriptome-wide Nm-seq on the poly A+ RNA of Raw264.7 macrophages after VSV infection . The Nm-seq profiles of wild-type Raw264.7 poly A+ RNA and VSV infected Raw264.7 poly A+ RNA were generated by deep sequencing using Illumina HiSeq4000 sequencer.
2022-04-05 | GSE185661 | GEO
Project description:The zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity.
2008-08-26 | GSE12545 | GEO
Project description:Growth factor independent-1 (Gfi1) is a zinc finger transcription factor with a SNAG amino-terminal repressor domain and is critically required for normal myelopoesis. Gfi1 is normally expressed in HSCs and induced during differentiation from CMPs to GMPs. Gfi1 loss-of-function mutation in mice and humans induces an arrest during myeloid differentiation and an absolute block to the formation mature neutrophils. This comparative microarray study was initiated to identify microRNAs which are potentially regulated by Gfi1 during granulopoiesis. The Gfi1 null allele from Orkin (deletion of exons 2 and 3) was backcrossed to B6 or Balb/c mice for at least 7 generations. RNA was isolated from low density bone marrow samples from Gfi1+/+ and Gfi1-/- B6 littermates, as well as Gfi1+/+ and Gfi1-/- Balb/c littermates.
2009-03-10 | E-GEOD-15077 | biostudies-arrayexpress