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:ObjectivesAlthough CpG methylation is well studied, mechanisms of non-CpG methylation in mammals remains elusive. Studying proteins with non-CpG cytosine methylation-sensitive DNA-binding, such as human CGGBP1, can unveil cytosine methylation regulatory mechanisms. Here we have resequenced a published genome-wide bisulfite sequencing library and analyzed it at base level resolution. CpG, CHG and CHH (where H is any nucleotide other than G) methylation states in non-targeting or CGGBP1-targeting shmiR lentivirus-transduced cells have been analyzed to identify how CGGBP1 regulates CpG and non-CpG methylation.ResultsWe report that CGGBP1 acts as a dynamic bimodal balancer of methylation. Both gain and loss of methylation observed upon CGGBP1 depletion were spatially overlapping at annotated functional regions and not identifiable with any sequence motifs but clearly associated with GC-skew. CGGBP1 depletion caused clustered methylation changes in cis, upstream of R-loop forming promoters. This was complemented by clustered occurrences of methylation changes in proximity of transcription start sites of known cytosine methylation regulatory genes, altered expression of which can regulate cytosine methylation in trans. Despite low coverage, our data provide reliable estimates of the spectrum of methylation changes regulated by CGGBP1 in all cytosine contexts genome-wide through a combination of cis and trans-acting mechanisms.
| 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:Dnmt3b is a tumor suppressor in oncogene-driven lymphoid and myeloid malignancies in mice. However, it is poorly understood whether reduced Dnmt3b activities can initiate malignant hematopoiesis. We modulated Dnmt3b activity in vivo by generating Dnmt3b+/− mice expressing one wild-type allele. Here, we analyzed methylation and gene expression in Dnmt3b+/- peripheral T-cell lymphomas (PTCLs).
2020-12-31 | GSE154270 | GEO