Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339495 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNMT3a is a de novo DNA methyltransferase expressed robustly after T cell activation that regulates plasticity of CD4+ T cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8+ T cell effector and memory fate decisions. While effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T cell intrinsic manner compared to wild-type animals. Rather than increasing plasticity of differentiated effector CD8+ T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells. This is attributed in part to ineffective repression of Tcf1 expression in knockout T cells, as DNMT3a localizes to the Tcf7 promoter and catalyzes its de novo methylation in early effector WT CD8+ T cells. This data identifies DNMT3a as a crucial regulator of CD8+ early effector cell differentiation and effector versus memory fate decisions. Examination of global genomic DNA methylation by MBD-seq in naïve CD8 T cells and CD8 T cells 8 days post Vaccinia-Ova infection, comparing OT1 TCR-Tg CD8 T cells isolated from WT and T cell conditional DNMT3a KO mice.
2016-08-20 | E-GEOD-85823 | biostudies-arrayexpress
Project description:DNMT3a is a de novo DNA methyltransferase expressed robustly after T cell activation that regulates plasticity of CD4+ T cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8+ T cell effector and memory fate decisions. While effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T cell intrinsic manner compared to wild-type animals. Rather than increasing plasticity of differentiated effector CD8+ T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells. This is attributed in part to ineffective repression of Tcf1 expression in knockout T cells, as DNMT3a localizes to the Tcf7 promoter and catalyzes its de novo methylation in early effector WT CD8+ T cells. This data identifies DNMT3a as a crucial regulator of CD8+ early effector cell differentiation and effector versus memory fate decisions.
2016-08-20 | GSE85823 | GEO
Project description:DNA methyltransferase 3A (DNMT3A) is the most frequently mutated gene in clonal hematopoiesis, indicating that it may be essential for hematopoietic differentiation. We therefore addressed the functional relevance of DNMT3A for hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) by knocking out either exon 2, 19, or 23. Directed differentiation towards mesenchymal stromal cells or hematopoietic progenitor cells (iHPCs) was only slightly reduced in exon 19-/- lines. Notably, exon 19-/- and exon 23-/- lines revealed absence of almost the entire de novo DNA methylation during differentiation. Despite the drastic effects on DNA methylation, there was no significant impact on gene expression of iHPCs. Notably, DNA methylation differences in acute myeloid leukemia with/without DNMT3A are related to iHPCs with/without DNMT3A knockout. Our results demonstrate that de novo DNA methylation during hematopoietic differentiation of iPSCs is almost entirely dependent on DNMT3A, while it has little impact on early cell-fate decisions.
2022-05-31 | GSE180402 | GEO
Project description:DNA methyltransferase 3A (DNMT3A) is the most frequently mutated gene in clonal hematopoiesis, indicating that it may be essential for hematopoietic differentiation. We therefore addressed the functional relevance of DNMT3A for hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) by knocking out either exon 2, 19, or 23. Directed differentiation towards mesenchymal stromal cells or hematopoietic progenitor cells (iHPCs) was only slightly reduced in exon 19-/- lines. Notably, exon 19-/- and exon 23-/- lines revealed absence of almost the entire de novo DNA methylation during differentiation. Despite the drastic effects on DNA methylation, there was no significant impact on gene expression of iHPCs. Notably, DNA methylation differences in acute myeloid leukemia with/without DNMT3A are related to iHPCs with/without DNMT3A knockout. Our results demonstrate that de novo DNA methylation during hematopoietic differentiation of iPSCs is almost entirely dependent on DNMT3A, while it has little impact on early cell-fate decisions.
2022-05-31 | GSE180403 | GEO
Project description:DNA methyltransferase 3a regulates CD8 T cell memory differentiation
2017-12-16 | GSE107150 | GEO
Project description:DNMT1 plays a major role in embryonic development as a maintenance methyltransferase. Although recent studies have shown that DNMT1 has de novo methylation activity, the detailed role of its function during embryonic development remains unclear. In this study, to further understand the role of DNMT1 de novo methylation, we performed RNA-seq on DNMT1/3A/3B triple knockout (TKO) mESCs and TKO mESCs expressing DNMT1 (TKO_FL).
2023-01-01 | GSE199124 | GEO
Project description:The transcription factor Inhibitor of DNA binding 2 (Id2) modulates T cell fate decisions but the molecular mechanism underpinning this regulation is unclear. Here, using whole genome mRNA analysis we show that loss of Id2 programs CD8+ T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. Our findings reveal that the Id2-E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation. Wild-type and Id2fl/flLckCre+ DbNP366-specific CD8+ T cells were isolated from the spleen of PR8-primed/HKx31-infected Ly5.2+Id2fl/flLckCre+:Ly5.1+ mixed bone marrow chimeric mice ten days after intranasal influenza infection and analysed by whole genome mRNA analysis. Three biological replicates of each genotype were subjected to microarray analysis.
2013-05-03 | E-GEOD-44141 | biostudies-arrayexpress
Project description:The de novo DNA methyltransferase 3A (DNMT3A) plays a pivotal role in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing of DNMT3A has characteristic epigenetic and functional sequels. Various transcripts of DNMT3A were either knocked down or overexpressed in human hematopoietic stem and progenitor cells resulting in complementary and transcript-specific DNA methylation (DNAm) and gene expression changes. Our results demonstrate that different splice variants of DNMT3A have distinct epigenetic and functional sequels.
2018-12-10 | GSE103007 | GEO
Project description:The de novo DNA methyltransferase 3A (DNMT3A) plays a pivotal role in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing of DNMT3A has characteristic epigenetic and functional sequels. Various transcripts of DNMT3A were either knocked down or overexpressed in human hematopoietic stem and progenitor cells resulting in complementary and transcript-specific DNA methylation (DNAm) and gene expression changes. Our results demonstrate that different splice variants of DNMT3A have distinct epigenetic and functional sequels.
2018-12-10 | GSE103006 | GEO
Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2. Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome. Keywords: Gene expression array-based The study was designed to examine the changes in gene expression between wild-type and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
2010-11-15 | E-GEOD-20015 | biostudies-arrayexpress