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.
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.
Project description:PML-RARa contributes to the development of APL through repression of genes important in myeloid development. Through a global approach, we have identified 2,979 high quality PML-RARa binding sites in ZnSO4 induced PR9 cells. By integration the gene expression data, we found that PML/RARa target genes are transcriptionally suppressed in primary APL cells and re-activated in ATRA treated NB4 cells. This SuperSeries is composed of the SubSeries listed below.
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.
Project description:GFI is a DNA binding transcriptional repressor that regulates myeloid differentiation. Here, we show that GFI1 interacts with the chromodomain helicase CHD4 and other components of the nucleosome remodeling and deacetylase (NuRD) complex. Our data demonstrated that GFI1 and GFI1/CHD4 complexes occupy sites of open chromatin enriched for histone marks associated with active transcription or different sets of genes that are either enriched for IRF1 or SPI-1 consensus binding sites. In addition, our study provided evidence that GFI1 affects the chromatin remodeling activity of the NuRD complex. Overall, our results indicate that GFI1/CHD4 complexes control chromatin openness and histone modifications differentially to regulate target genes, which govern the immune response, nucleosome organization, or metabolic processes.