Identification of genomic associations of transcription factors BCL11B, Ikaros, and Mi2beta in primary mouse thymocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59826 | GEO | 2021/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Bcl11b hypomorphic mutant thymocytes
| PRJNA356604 | ENA
Project description:Review on the role of Bcl11b in thymus and periphery and impact on diseases RNA was extracted from DP thymocytes of bcl11bf/fCd4cre/tcra-/- and tcra-/- mice. Tcra-/- mice only have preselected DP thymocytes. Such mice were used to determine the role of Bcl11b before selection, considering the defective positive selection in bcl11bf/fcd4cre mice. RNA was isolated and submitted for library generation and microarray analysis to determine expression profile of bcl11b-/- preselected DP thymocytes.
2014-04-12 | E-GEOD-56714 | biostudies-arrayexpress
Project description:T-cell receptor (TCR) signals play a critical role in guiding selected thymocytes to distinct lineages by activating genes for transcription factors, such as ThPOK and Runx3, for the helper- or cytotoxic-lineage, respectively. Here we show that Bcl11b, known as an early T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3. Loss of Bcl11b resulted in premature and random expression of these specification factors, leading to lineage scrambling that was disconnected from TCR restriction by MHC. Early Thpok repression by Bcl11b is independent of its known transcriptional silencer, but requires the C-terminal zinc-finger of Bcl11b. Collectively, our findings shed new light on the role of Bcl11b in priming lineage-specifying genes to integrate TCR signals into a subsequent developmental program that dissects effector lineages.
2017-07-20 | GSE90949 | 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:T-cell receptor (TCR) signals play a critical role in guiding selected thymocytes to distinct lineages by activating genes for transcription factors, such as ThPOK and Runx3, for the helper- or cytotoxic-lineage, respectively. Here we show that Bcl11b, known as an early T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3. Loss of Bcl11b resulted in premature and random expression of these specification factors, leading to lineage scrambling that was disconnected from TCR restriction by MHC. Early Thpok repression by Bcl11b is independent of its known transcriptional silencer, but requires the C-terminal zinc-finger of Bcl11b. Collectively, our findings shed new light on the role of Bcl11b in priming lineage-specifying genes to integrate TCR signals into a subsequent developmental program that dissects effector lineages.
2017-07-20 | GSE90989 | GEO
Project description:Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks. We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage. 8 samples (mouse DP thymocytes from wt, and different stage after Ikaros inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0. Examination of different histone modifications and binding sites for Ikaros, Mi2beta in wild type DP thymocytes, and Ikaros knockout thymocytes.
2011-11-13 | E-GEOD-32311 | biostudies-arrayexpress
Project description:The aim of the experiment was to visualize genes under the control of Ikaros during early T cell development. We used mice carrying floxed Ikaros alleles that were crossed with the Rosa26-CreERT2 mice, and which were injected with tamoxifen for 4 days. DN4 thymocytes were sorted from 4 mice (5-6 week-old) which are positive or not for the Rosa26-CreERT2 transgene.
2013-04-17 | GSE46093 | GEO
Project description:The aim of the experiment was to visualize genes under the control of Ikaros during early T cell development. We used mice carrying floxed Ikaros alleles that were crossed with the Rosa26-CreERT2 mice, and which were injected with tamoxifen for 4 days. DN4 thymocytes were sorted from 4 mice (5-6 week-old) which are positive or not for the Rosa26-CreERT2 transgene. DN4 cells were sorted from 2 Ikf/f Rosa26-CreERT2+ mice and 2 Ikf/f mice, which were all treated with tamoxifen for 4 days. Loss of Ikaros was confirmed in sorted cells from the Ikf/f Rosa26-CreERT2+ mice by western blot. Gene expression profiles were determined on total RNA from sorted cells with Affymetrix Mouse Gene arrays.
2013-04-17 | E-GEOD-46093 | biostudies-arrayexpress
Project description:The C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors. Ikaros RNA-Seq from double positive thymocytes comparing wt (n=2), Ikaros-ZnF1-/- mutant (n=2) and Ikaros-ZnF4-/- mutant (n=2)
2013-09-08 | E-GEOD-47496 | biostudies-arrayexpress
Project description:To understand the impact of Bcl11b N440K variant on the DNA recognition by TCF1, we performed ChIP-seq of Bcl11b with Bcl11b+/+ and Bcl11b+/N440K thymocytes.
2024-09-27 | GSE263016 | GEO