Similar Datasets
Project description:To study the effect of transcription factor GFI1 on lung cancer cells, we overexpressed GFI1 in A549 cells and performed RNA-seq. Moreover, control and GFI1-expressing A549 cells that were forced into suspension for 48hrs were used performed RNA-seq.
2022-09-14 | GSE165307 | GEO
Project description:Activation of GFI1-super-enhancer (GFI1-SE) by a LSD1 inhibitor NCD38 was relevant to myeloid differentiation and antileukemia effect in human erythroleukemia cells (HEL cells). Thus, we investigated the role of GFI1-SE upon NCD38 treatment in HEL cells. We established three independent sublines with bi-allelic deletion of GFI1-SE (CCE2 #114, #141, and #216) using CRISPR-Cas9 genome editing system in HEL cells and a classical limiting dilution method. Control sublines (Ctrl C1, C2, and C5) were established by transfection of parent vector and limiting dilution. After treatment of each subline with DMSO or NCD38 (LSD1i) for 24 hours, these gene expression profiling data were obtained.
2020-03-31 | GSE128400 | GEO
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:Innate type-2 lymphocytes (ILC2s) are a newly described cell type whose biology and contribution to disease are poorly understood. We are interested in investigating the role of the transcription factor Gfi1 in ILC2s, which appear to be a prominent source of IL-5 and IL-13 during type-2 immune responses. We have compelling evidence demonstrating a critical role for Gfi1 in the development and effector state of ILC2s. We would like to elucidate the molecular role of Gfi1 in ILC2s by identifying Gfi1-regulated genes by microarray analysis. Gfi1+/+ or Gfi1GFP/GFP (a GFP cassette has been 'knocked-in' to the Gfi1 locus and thus functions both as a surrogate for Gfi1 promoter activity and as a loss-of-function allele) mice were injected with IL-25 once daily for 4 days. On day 5, ILC2s (Lin-/Sca-1+/ICOS+/CD127+/c-Kit+) were sorted from the mesenteric lymph nodes of Gfi1+/+ (3 mice/sample were pooled together) or Gfi1-/- mice (6 mice/sample were pooled together) and cultured for 6 days in RPMI 1640, 10% FBS, Gln, P/S, 2ME, IL-2 (50ng/ml), IL-7 (10ng/ml), and IL-25 (50ng/ml). Whole RNA was harvested on day 6 via the RNeasy kit (Qiagen).
2013-10-20 | E-GEOD-45621 | biostudies-arrayexpress
Project description:GFI1 is a transcriptional repressor protein that represses the transcription by mediating chromatin modifications such as histone demethylation, methylation and deacetylation of target genes. The genes with significant open chromatin configuration in the promoter and enhancer regions of GFI1-KI and GFI1-KD mice are identified in this study. This aids in the identification of unique additional genes that might be GFI1 protein's potential targets. We showed a significant open chromatin configuration of Foxo1 promoter and enhancer regions with reduced GFI1 expression. This gives additional support for hypothesising FOXO1 as a target gene of GFI1, along with the data from CHIPseq and RNAseq analysis.
2023-12-01 | GSE197214 | GEO
Project description:In order to indentify the transcriptional differences between GFI1 KD and GFI1 KO mice that may account for differences in occurence of AML between these mice, we performed exresiion profiling by RNA-Seq on healthy young and old mice mice from both genotypes. In the case of GFI1 KD, the older mice had developped AML whereas KO mice of comparable ages did not.
2018-06-01 | GSE102957 | 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. 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:To determine the impact of inhibition of KDM1A/LSD1 through genetic manipulation by CRISPR/Cas9 or inducible shRNA or following treatment with irreversible LSD1 inhibitor INCB059872 on global transcriptomic profile in AML and post-MPN sAML cells. To determine the impact of GFI1 knockdown on global transcriptomic profile in AML cells.
2021-05-26 | GSE160303 | GEO
Project description:Innate type-2 lymphocytes (ILC2s) are a newly described cell type whose biology and contribution to disease are poorly understood. We are interested in investigating the role of the transcription factor Gfi1 in ILC2s, which appear to be a prominent source of IL-5 and IL-13 during type-2 immune responses. We have compelling evidence demonstrating a critical role for Gfi1 in the development and effector state of ILC2s. We would like to elucidate the molecular role of Gfi1 in ILC2s by identifying Gfi1-regulated genes by microarray analysis.
2013-10-20 | GSE45621 | GEO
Project description:To investigate the genes regulated by the transcription factor GFI1 in lung cancer cells, we overexpressed GFI1-Flag in A549 cells and performed ChIP-Seq with anti-Flag affinity gel.
2022-09-14 | GSE164984 | GEO