Identification of GFI1 target genes in human lung adenocarcinoma cell line A549 [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164984 | GEO | 2022/09/14
REPOSITORIES: GEO
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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.
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Project description:RNAseq of control and GFI1-expressing A549
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Project description:The immunoprecipitates captured by Flag M2 affinity gel from USP12-Flag-expressed A549 cells were separated by SDS-PAGE. The gel was excised, digested with trypsin, and then subjected to LC-MS/MS analysis.
2021-07-09 | MSV000087785 | MassIVE
Project description:Identification of GFI1 target genes in human lung adenocarcinoma cell line A549 [ChIP-seq]
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Project description:MDS is characterized by a disturbed function of the myeloid lineage of the hematopoietic system that may transform to AML, a malignant disease of the myeloid compartment. Epigenetic and genetic aberrations contribute to the initiation and progression of MDS/AML. GFI1 is a transcriptional repressor, which regulates expression of its target genes by, among other approaches, recruiting HDACs to its target genes to remove histone 3 lysine 9 (H3K9) acetylation, a marker for active gene expression. Low levels of GFI1 expression and deletion of one GFI1 allele contribute to MDS/AML development in human patients and are associated with a specific gene expression signature and inferior prognosis. To explore the mechanism behind this, we used a mouse strain, which expresses GFI1 only at 5-10% of the normal level (GFI1-Knock-down (KD)). Knock-down of GFI1 or loss of one murine Gfi1 allele reduced latency and increased incidence of AML in different murine models of human MDS/AML development. On the epigenetic level, KD of Gfi1 lead to increased amount of H3K9 acetylation, resulting in increased expression of genes involved in AML development. On a translational level both murine as well as human AML cells with low expression of GFI1 are resistant to standard epigenetic therapy. We show that treatment with histone acetyltransferase inhibitors might be a novel treatment approach for low Gfi1-expressing blast cells. GFI1 has a dose dependent role in myeloid malignancies and is a biomarker for therapeutic intervention. We used microarrays to detail the global programme of gene expression in bone marrow cells of Nup98HoxD13 leucemic mice and identified distinct classes of up-regulated genes during this process. Bone marrow cells of leukemic mice (from KI & KD Nup98HoxD13 mice) were collected for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of leukemic cell population, so we took samples of mice which had the same age.
2016-07-31 | E-GEOD-72489 | biostudies-arrayexpress
Project description:Using (conditional) Gfi1 knock-out mice we show that ablation of the transcriptional repressor Gfi1 cures mice from lymphoid leukemia and reduces the expansion of primary human T-ALL xenografts in mice. We find that Gfi1 alters the p53 dependent transcriptional activation of a substantial subset of known p53 target genes and thus sets a threshold for cell death. We used Affymetrix mouse Gene-1.0-ST arrays to define the changes in the gene expression pattern of wt or Gfi1-KO thymocytes (Gfi1-fl/fl X MX-CRE, induced by pIpC) that were either untreated (WT, GfiKO thymocytes), irradiated (WT_irr, Gfi1KO_irr), ENU transformed (WT_Tum, Gfi1KO_Tum), or transformed by Notch1-CT and ENU-induced to enhance tumorigenesis (WT_Notch_Tum, Gfi1KO_Notch_Tum). The study should determine how loss of Gfi1 alters the gene expression pattern in irradiated or tumor derived thymocytes
2012-10-03 | E-GEOD-32910 | biostudies-arrayexpress
Project description:Drugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associates with Gfi1, and that these proteins cooperate to inhibit genes involved in neuronal commitment and differentiation. We also show that Lsd1 is essential for Gfi1-mediated transformation: Gfi1 proteins that cannot recruit Lsd1 are unable to drive tumorigenesis and genetic ablation of Lsd1 markedly impairs tumor growth in vivo. Finally, pharmacological inhibitors of Lsd1 potently inhibit growth of Gfi1-driven tumors. These studies provide important insight into the mechanisms by which Gfi1 contributes to tumorigenesis, and identify Lsd1 inhibitors as promising therapeutic agents for Gfi1-driven medulloblastoma.
2018-12-07 | GSE123409 | GEO
Project description:Drugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associates with Gfi1, and that these proteins cooperate to inhibit genes involved in neuronal commitment and differentiation. We also show that Lsd1 is essential for Gfi1-mediated transformation: Gfi1 proteins that cannot recruit Lsd1 are unable to drive tumorigenesis and genetic ablation of Lsd1 markedly impairs tumor growth in vivo. Finally, pharmacological inhibitors of Lsd1 potently inhibit growth of Gfi1-driven tumors. These studies provide important insight into the mechanisms by which Gfi1 contributes to tumorigenesis, and identify Lsd1 inhibitors as promising therapeutic agents for Gfi1-driven medulloblastoma. ChIP-seq data generated for n=2 MG (Myc/Gfi1) murine medulloblastomas. ChIP was independently performed for Gfi1 and Lsd1 on the same chromatin extracts.
2018-12-15 | GSE123870 | GEO
Project description:MDS is characterized by a disturbed function of the myeloid lineage of the hematopoietic system that may transform to AML, a malignant disease of the myeloid compartment. Epigenetic and genetic aberrations contribute to the initiation and progression of MDS/AML. GFI1 is a transcriptional repressor, which regulates expression of its target genes by, among other approaches, recruiting HDACs to its target genes to remove histone 3 lysine 9 (H3K9) acetylation, a marker for active gene expression. Low levels of GFI1 expression and deletion of one GFI1 allele contribute to MDS/AML development in human patients and are associated with a specific gene expression signature and inferior prognosis. To explore the mechanism behind this, we used a mouse strain, which expresses GFI1 only at 5-10% of the normal level (GFI1-Knock-down (KD)). Knock-down of GFI1 or loss of one murine Gfi1 allele reduced latency and increased incidence of AML in different murine models of human MDS/AML development. On the epigenetic level, KD of Gfi1 lead to increased amount of H3K9 acetylation, resulting in increased expression of genes involved in AML development. On a translational level both murine as well as human AML cells with low expression of GFI1 are resistant to standard epigenetic therapy. We show that treatment with histone acetyltransferase inhibitors might be a novel treatment approach for low Gfi1-expressing blast cells. GFI1 has a dose dependent role in myeloid malignancies and is a biomarker for therapeutic intervention. We carried out ChIP-Seq Analysis of H3K9Ac and RNA-Seq in leukemic cells from mice expressing reduced levels of Gfi1 compared to controls expressing normal levels of the factor.
2016-05-12 | GSE72671 | 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