Similar Datasets
Project description:Dnmt3b is a DNA methyltransferase, an enzyme which methylates genomic DNA, contributes to genomic stability and transcriptional regulation. Inactivation of Dnmt3b in mice results in embryonic lethality at E13.5. It is however unclear which activities are responsible for this phenomenon. Here, we analyzed methylation and gene expression in Dnmt3b+/+ (WT), Dnmt3b-/- (3bKO) and Dnmt3bCI/CI (3bKI) embryos at E11.5.
2019-08-19 | GSE132952 | GEO
Project description:Cortical neurogenesis requires the fine tuning of gene expression, modulated by genetic and epigenetic mechanisms during the entire process. Among the epigenetic factors expressed by the proliferative radial glia cells, Prdm16 has been shown to play a key role in cell proliferation. We found Prdm16 to be expressed exclusively by radial glia cells and to be rapidly turned off in newborn neurons. Predictably, Prdm16-null mice displayed a decrease in cortical thickness as a consequence of an impairment in self-renewal of radial glia cells. Conversely, Prdm16-overexpressing neural progenitors showed an increase in self-renewal activity and failed to complete differentiation. Lineage restriction in differentiating stem cells is achieved by chromatin modifications such as histone modifications and DNA methylation along the promoters of stemness-related genes. We found the expression of the DNA methyltransferase Dnmt3b to be inversely correlated to that of Prdm16. Loss and gain of Prdm16 function leaded to an up- and down-regulation of Dnmt3b, respectively. Functional analysis confirmed Prdm16 competence to repress Dnmt3b expression. Finally, IUE of Prdm16 together with Dnmt3b rescued the increase in radial glia cells self-renewal observed with Prdm16 alone. Thus, Prdm16 may play a crucial role in ensuring neural progenitor self-renewal, mainly through the maintenance of the unmethylated state of stemness-related genes.
2022-05-25 | GSE59574 | GEO
Project description:Cortical neurogenesis requires the fine tuning of gene expression, modulated by genetic and epigenetic mechanisms during the entire process. Among the epigenetic factors expressed by the proliferative radial glia cells, Prdm16 has been shown to play a key role in cell proliferation. We found Prdm16 to be expressed exclusively by radial glia cells and to be rapidly turned off in newborn neurons. Predictably, Prdm16-null mice displayed a decrease in cortical thickness as a consequence of an impairment in self-renewal of radial glia cells. Conversely, Prdm16-overexpressing neural progenitors showed an increase in self-renewal activity and failed to complete differentiation. Lineage restriction in differentiating stem cells is achieved by chromatin modifications such as histone modifications and DNA methylation along the promoters of stemness-related genes. We found the expression of the DNA methyltransferase Dnmt3b to be inversely correlated to that of Prdm16. Loss and gain of Prdm16 function leaded to an up- and down-regulation of Dnmt3b, respectively. Functional analysis confirmed Prdm16 competence to repress Dnmt3b expression. Finally, IUE of Prdm16 together with Dnmt3b rescued the increase in radial glia cells self-renewal observed with Prdm16 alone. Thus, Prdm16 may play a crucial role in ensuring neural progenitor self-renewal, mainly through the maintenance of the unmethylated state of stemness-related genes.
2022-05-25 | GSE77697 | GEO
Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knockin mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function.
2016-01-11 | E-GEOD-71039 | biostudies-arrayexpress
Project description: Not available
| S-EPMC6027561 | biostudies-literature
Project description:Here, we analyzed global gene expression changes that were associated with over expression of Dnmt3b in MLL-AF9 induced leukemias using the Affymetrix microarray platform. Changes in global gene expression were determined with Affymetrix microarrays in MLL-AF9 induced leukemias over expressing Dnmt3b.
2016-01-11 | E-GEOD-71040 | biostudies-arrayexpress
Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function.
2016-01-11 | GSE71039 | GEO
Project description:In order to assess the impact of sphingosine kinase-1 (SK1) expression on melanoma growth, stable SK1 knockdown cells were generated by shRNA, using Yumm 1.7 cells derived from spontaneous murine melanoma driven by Braf activation as well as Pten and Cdkn2a inactivation. Two cell lines silenced for SK1 (shSK1(1) and shSK1(2)) were obtained.
2019-12-17 | PXD016535 | Pride
Project description:Dnmt3b is a DNA methytransferase which is an enzyme that methylated genomic DNA which contributes to genomic stability and transcriptional regulation. We genetically inactivated Dnmt3b in the hematopoeitic compartment in the context of MYC overexpression and analysed the resulting thymic lymphomas.
2011-11-21 | E-GEOD-33849 | biostudies-arrayexpress
Project description:The methylation status of colon epithelial cells was profiled in wild type mice and mice expressing a Dnmt3b transgene. Genome-scale methylation profiles were generated using reduced representation bisulfite sequencing (RRBS), with CpG methylation scored by promoter and also summarized by gene. Dnmt3b expression is associated with a strong increase in de novo methylation of a discrete subset of "methylation sensitive" genes which show a strong concordance with genes methylated in human colon cancer. These results, together with further analysis, indicate that colon epithelial cell methylation in the Dnmt3b mouse model predicts DNA methylation of human colon cancer with high confidence. Three each of Dnmt3b-induced and control mice, each split into two fractions.
2011-10-25 | E-GEOD-26758 | biostudies-arrayexpress