Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148177 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression data from normal thymocytes, 24 day pre-tumor Dnmt3b-deficient thymocytes, Wild-Type Tumors, and Dnmt3b-deficient Tumors
| PRJNA144039 | ENA
Project description:The de novo DNA methyltransferase DNMT3B functions in establishing DNA methylation patterns during development. We performed RNAi knockdown of DNMT3B in human embryonic stem cells (ESCs) in order to investigate the mechanistic contribution of DNMT3B on DNA methylation and early neuronal differentiation. Genome-wide analyses of DNA methylation by MethylC-seq identified novel regions of hypomethylation in the DNMT3B knockdowns along the X chromosome as well as pericentromeric regions, rather than changes to specific dysregulated gene promoters. While DNMT3B was not required for early neuroepithelium specification, DNMT3B deficient neuroepithelium exhibited accelerated maturation with earlier expression of mature neuronal markers (such as NEUROD1) and early neuronal regional specifiers (such as neural crest) relative to normal ESCs. Our results suggest that DNMT3B mediates large-scale methylation patterns in human ESCs and that DNMT3B deficiency alters the timing of neuronal maturational differentiation in human neuronal cultures. Examined DNA methylation in human embryonic stem cells, both with and without DNMT3B knockdown
2012-03-27 | E-GEOD-32268 | biostudies-arrayexpress
Project description:Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed transgenic mice expressing DNMT3B7, a common truncated DNMT3B isoform in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Eμ−myc animals. Eμ-myc/DNMT3B7 lymphomas have more chromosomal rearrangements, increased global methylation levels, and more locus-specific perturbations in DNA methylation patterns compared to Eμ-myc lymphomas. Our results demonstrate that a truncated DNMT3B protein can alter tumorigenesis, suggesting a similar role in human tumors. Direct comparison of DNA methylation in lymphoma samples from Eu-Myc vs Eu-Myc/Dnmt3b7 mice.
2010-07-30 | E-GEOD-21273 | biostudies-arrayexpress
Project description:The de novo DNA methyltransferase DNMT3B functions in establishing DNA methylation patterns during development. We performed RNAi knockdown of DNMT3B in human embryonic stem cells (ESCs) in order to investigate the mechanistic contribution of DNMT3B on DNA methylation and early neuronal differentiation. Genome-wide analyses of DNA methylation by MethylC-seq identified novel regions of hypomethylation in the DNMT3B knockdowns along the X chromosome as well as pericentromeric regions, rather than changes to specific dysregulated gene promoters. While DNMT3B was not required for early neuroepithelium specification, DNMT3B deficient neuroepithelium exhibited accelerated maturation with earlier expression of mature neuronal markers (such as NEUROD1) and early neuronal regional specifiers (such as neural crest) relative to normal ESCs. Our results suggest that DNMT3B mediates large-scale methylation patterns in human ESCs and that DNMT3B deficiency alters the timing of neuronal maturational differentiation in human neuronal cultures.
2012-03-28 | GSE32268 | GEO
Project description:Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed transgenic mice expressing DNMT3B7, a common truncated DNMT3B isoform in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Eμ−myc animals. Eμ-myc/DNMT3B7 lymphomas have more chromosomal rearrangements, increased global methylation levels, and more locus-specific perturbations in DNA methylation patterns compared to Eμ-myc lymphomas. Our results demonstrate that a truncated DNMT3B protein can alter tumorigenesis, suggesting a similar role in human tumors.
2010-07-30 | GSE21273 | GEO
Project description:Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. Here, we report that most of lung cancer cell lines tested expressed predominantly ∆DNMT3B-del whereas normal bronchial epithelial cells expressed equal quantities of ∆DNMT3B and ∆DNMT3B-del. We demonstrate biological impacts of ∆DNMT3B4-del, a ∆DNMT3B-del isoform, in a transgenic mouse model. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. In patients with non-small cell lung cancer, 83% of the primary tumors expressed predominantly ∆DNMT3B-del. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation during lung tumorigenesis.
2017-02-09 | GSE68922 | GEO
Project description:To better characterize the effects of USP7 on DNA methylation, we performed reduced representative bisulfite sequencing (RRBS) analysis for a genome-wide comparison of DNA methylation in wild-type, USP7-KO-1, DNMT3A/3B-DKO and DNMT3A/DNMT3B/USP7-TKO HeLa cell lines. RRBS analysis showed increased DNA methylation in USK7-KO cells and loss of USP7 elevates DNA methylation on pre-existing sites and de novo methylation.
2020-09-07 | GSE136159 | GEO
Project description:Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transduction of defined transcription factors and involves dynamic changes in DNA methylation. While the reprogramming of somatic cells is accompanied by de-methylation of pluripotency genes, the functional importance of de novo DNA methylation has not been clarified. Here, using loss-of-function studies, we generated iPSCs from fibroblasts that were deficient in de novo DNA methylation mediated by Dnmt3a and Dnmt3b. These iPSCs reactivated pluripotency genes, underwent self-renewal and showed restricted developmental potential which was rescued upon re-introduction of Dnmt3a and Dnmt3b. We conclude that de novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells. RNA levels of Dnmt3ab deficient iPSC cell lines were compared to control iPSC cell lines
2011-05-16 | E-GEOD-28629 | biostudies-arrayexpress
Project description:The TAL1/SCL and LMO1 oncogenic transcription factors establish a pre-leukemic state by reprogramming thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Pre-TCR signaling accelerates the progression to T-cell acute lymphoblastic leukemia (T-ALL). To directly address the importance of pre-TCR signaling in driving progression to T-ALL, we leverage on Cd3-deficient mice in which pre-TCR signaling and progression through β-selection is abrogated. In the absence of pre-TCR signaling in Cd3ε-deficient SCL-LMO1 transgenic mice, T-ALL onset is delayed by 150 days. Despite the absence of pre-TCR/CD3 signaling in these mice, we show that leukemic thymocytes exhibit the gene expression profiles of thymocytes that have undergone β-selection, i.e. exhibiting a re-activation of pre-TCR-driven proliferation signature, and a down regulation of HEB/TCF12 target genes. Lastly, monoallelic deletion of Heb is sufficient to accelerate T-ALL onset in Cd3ε-deficient SCL-LMO1 transgenic mice. Together, these results underscore the role of HEB/TCF12 as a tumor suppressor in T-ALL.
2022-03-27 | GSE198506 | GEO
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