Ikaros regulates gene expression downstream of TCR signaling
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79219 | GEO | 2019/03/14
REPOSITORIES: GEO
Similar Datasets
Project description:Ikaros is critical in setting the threshold for T-cell activation and proliferation. Here we used mature CD8+ T cells from mice lacking the zinc finger 4 of Ikaros (Ikaros-Zn4-/-) to study its role in regulating gene expression at early time points after T-cell receptor stimulation.
2019-03-14 | GSE79221 | GEO
Project description:T cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related, and the activation of lymphocyte-specific programs. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor interacts with the Polycomb Repressive Complex 2 (PRC2) in CD4-CD8- thymocytes, and allows its binding to >200 developmentally-regulated genes, many of which are expressed in hematopoietic stem cells. Loss of Ikaros in CD4-CD8- cells leads to diminished histone H3 Lys27 (H3K27) trimethylation and ectopic expression of these genes. Ikaros binding triggers PRC2 recruitment and H3K27 trimethylation. Furthermore, Ikaros interacts with PRC2 independently of the Nucleosome Remodeling and Deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells. Genome-wide comparison of different histone modifications, Ikaros, Suz12 and NuRD binding in different stages of T cell development in WT and Ikaros mutant mice. Profiling of H3K27me3 in DN1, DN2, DN3, DN4 and DP thymocytes and hematopoietic stem and progenitor cells (LSK cells) of WT and Ikaros mutant mice. Profiling of H3K4me3 and H3ac in WT and Ikaros mutant DP thymocytes. Global analysis of Ikaros binding in WT DN3, DN4 and DP cells, Suz12 binding in WT and Ikaros mutant DN3 cells, and Mta2 and Mi2beta binding in WT DN3 cells. Genome-wide profiling of Ikaros binding and H3K27me3 upon Ikaros activation in Ikaros-deficient leukemic T cells.
2015-11-03 | E-GEOD-61148 | biostudies-arrayexpress
Project description:Ikaros encodes a transcription factor that functions as a tumor suppressor in T-ALL. The mechanisms through which Ikaros regulates gene expression and cellular proliferation in T-ALL are unknown. Re-introduction of Ikaros into Ikaros-null T-ALL cells results in cessation of cellular proliferation and induction of T-cell differentiation. We performed dynamic global epigenomic and gene expression analyses to determine the role of Ikaros in tumor suppression during this process. Our results identified novel Ikaros functions in the epigenetic regulation of gene expression: Ikaros directly regulates de novo formation and depletion of enhancers, as well as de novo formation of active enhancers and activation of poised enhancers; Ikaros directly induces the formation of super-enhancers; and Ikaros demonstrates pioneering activity by directly regulating chromatin accessibility. Dynamic analyses demonstrate the long-lasting effect of Ikaros DNA binding on enhancer activation, de novo formation of enhancers and super-enhancers, and chromatin accessibility. Ikaros induces profound, global re-distribution of HDAC1 via recruitment of HDAC1 to promoter and enhancer regions of different target genes. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and Ikaros-induced enhancers, and that are responsible for the cessation of proliferation and induction of T-cell differentiation in T-ALL cells.
2019-03-31 | GSE126567 | GEO
Project description:Ikaros encodes a transcription factor that functions as a tumor suppressor in T-ALL. The mechanisms through which Ikaros regulates gene expression and cellular proliferation in T-ALL are unknown. Re-introduction of Ikaros into Ikaros-null T-ALL cells results in cessation of cellular proliferation and induction of T-cell differentiation. We performed dynamic global epigenomic and gene expression analyses to determine the role of Ikaros in tumor suppression during this process. Our results identified novel Ikaros functions in the epigenetic regulation of gene expression: Ikaros directly regulates de novo formation and depletion of enhancers, as well as de novo formation of active enhancers and activation of poised enhancers; Ikaros directly induces the formation of super-enhancers; and Ikaros demonstrates pioneering activity by directly regulating chromatin accessibility. Dynamic analyses demonstrate the long-lasting effect of Ikaros DNA binding on enhancer activation, de novo formation of enhancers and super-enhancers, and chromatin accessibility. Ikaros induces profound, global re-distribution of HDAC1 via recruitment of HDAC1 to promoter and enhancer regions of different target genes. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and Ikaros-induced enhancers, and that are responsible for the cessation of proliferation and induction of T-cell differentiation in T-ALL cells.
2019-03-31 | GSE126391 | GEO
Project description:Ikaros encodes a transcription factor that functions as a tumor suppressor in T-ALL. The mechanisms through which Ikaros regulates gene expression and cellular proliferation in T-ALL are unknown. Re-introduction of Ikaros into Ikaros-null T-ALL cells results in cessation of cellular proliferation and induction of T-cell differentiation. We performed dynamic global epigenomic and gene expression analyses to determine the role of Ikaros in tumor suppression during this process. Our results identified novel Ikaros functions in the epigenetic regulation of gene expression: Ikaros directly regulates de novo formation and depletion of enhancers, as well as de novo formation of active enhancers and activation of poised enhancers; Ikaros directly induces the formation of super-enhancers; and Ikaros demonstrates pioneering activity by directly regulating chromatin accessibility. Dynamic analyses demonstrate the long-lasting effect of Ikaros DNA binding on enhancer activation, de novo formation of enhancers and super-enhancers, and chromatin accessibility. Ikaros induces profound, global re-distribution of HDAC1 via recruitment of HDAC1 to promoter and enhancer regions of different target genes. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and Ikaros-induced enhancers, and that are responsible for the cessation of proliferation and induction of T-cell differentiation in T-ALL cells.
2019-03-31 | GSE126568 | GEO
Project description:Ikaros functions as a master regulator of lymphocyte differentiation and a tumor suppressor. Ikaros binds DNA and regulates gene expression by chromatin remodeling. Mechanisms of Ikaros-mediated tumor suppression are unknown. Here we examined genome-wide occupancy of Ikaros and histone deacetylase 1 (HDAC1) and Histone midificaition markers in human leukemia, and found that the Ikaros and HDAC1 showed similar binding partern and HDAC1âDNA interactions are associated with the presence of bivalent chromatin, and the recruitment of HDAC1 by Ikaros is associated with bivalent chromatin at Ikaros target genes. Examine the genome-wide binding of Ikaros, HDAC1, H3K9me3, H3K9ac, H3K27me3, H3K4me3 and H3K36me3 in Nalm6 ALL leukemia cells.
2015-11-03 | E-GEOD-44217 | biostudies-arrayexpress
Project description:T cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related, and the activation of lymphocyte-specific programs. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor interacts with the Polycomb Repressive Complex 2 (PRC2) in CD4-CD8- thymocytes, and allows its binding to >200 developmentally-regulated genes, many of which are expressed in hematopoietic stem cells. Loss of Ikaros in CD4-CD8- cells leads to diminished histone H3 Lys27 (H3K27) trimethylation and ectopic expression of these genes. Ikaros binding triggers PRC2 recruitment and H3K27 trimethylation. Furthermore, Ikaros interacts with PRC2 independently of the Nucleosome Remodeling and Deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells.
2015-11-03 | GSE61148 | GEO
Project description:Ikaros functions as a master regulator of lymphocyte differentiation and a tumor suppressor. Ikaros binds DNA and regulates gene expression by chromatin remodeling. Mechanisms of Ikaros-mediated tumor suppression are unknown. Here we examined genome-wide occupancy of Ikaros and histone deacetylase 1 (HDAC1) and Histone midificaition markers in human leukemia, and found that the Ikaros and HDAC1 showed similar binding partern and HDAC1–DNA interactions are associated with the presence of bivalent chromatin, and the recruitment of HDAC1 by Ikaros is associated with bivalent chromatin at Ikaros target genes.
2015-11-03 | GSE44217 | GEO
Project description:The aim of the experiment was to compare to single and combined effect of Ikaros activation and IL-7 withdrawal in the Ikaros-null pre-B cell line BH1 The mouse BH1 pre-B cell line was transduced with retroviruses encoding Bcl2 and an Ikaros-estrogen receptor fusion protein. Doubly transduced cells were purified by FACS (BH1-Bcl2-Ik1ER). The transcriptome of these cells was analyzed at time 0, and after 6h and 24h of induction of Ikaros activity with 4-hydroxytamoxifen (4OHT) and/or withdrawal of IL-7. Samples from 2 independent experiments were analyzed (exp1 and exp2).
2013-11-30 | E-GEOD-51350 | biostudies-arrayexpress
Project description:The aim of the experiment was to compare to single and combined effect of Ikaros activation and IL-7 withdrawal in the Ikaros-null pre-B cell line BH1
2013-11-30 | GSE51350 | GEO