DNMT1 KNOCKOUT IN MURINE LIVER (expression)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67734 | GEO | 2016/04/01
SECONDARY ACCESSION(S): PRJNA280859
REPOSITORIES: GEO
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Project description:Methylation profilingof isolated hepatocytes after DNMT1 knock down. DNMT1 KO versus control livers at week 4, 8 and 20.
2016-04-01 | GSE67767 | GEO
Project description:Methylation profilingof isolated hepatocytes after DNMT1 knock down. DNMT1 KO versus control livers at week 4, 8 and 20. 18 samples analyzed
2016-04-01 | E-GEOD-67767 | biostudies-arrayexpress
Project description:Gene expression analysis of liver after DNMT1 knock down. DNMT1 KO versus control livers at week 4, 8 and 20. 24 Samples analyzed
2016-04-01 | E-GEOD-67734 | biostudies-arrayexpress
Project description:To identify the target genes of Dnmt1 in skeletal muscle satellite cells, we generated satellite cell specific Dnmt1 KO using Pax7-CreERT2 and Dnmt1 flox mice. After Tamoxifen (cKO) or vehicle (Control) treatment for 5 consecutive days, mice were euthanized and muscle satellite cells were collected by FACS sorting and total RNA were extracted.
2021-01-08 | GSE156978 | GEO
Project description:We report that Dnmt1 is crucial during perinatal intestinal development. Loss of Dnmt1 in intervillus progenitor cells causes global hypomethylation, DNA damage, premature differentiation, and apoptosis, and consequently, loss of nascent villi. We further confirm the critical role for Dnmt1 during crypt development using the in vitro organoid culture system, and illustrate a clear differential requirement for Dnmt1 in immature versus mature organoids. These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts.
2015-05-29 | GSE67363 | GEO
Project description:Purpose: Epigenetic regulation contributes to pathogenesis of neurondegenerative disease. We found that dis-regulation of a 242-gene subnetwork related to DNA methylation regulated neuronal differentiation are common in AD and HD. There are two DNA methyltransferases, DNMT1 and DNMT3A, in the subnetwork. DNMT1 is one of top hub genes in the network and likely to play a key regulatory role in the subnetwork. To validate that DNMT1 is a key regulator for the subnetwork, and DNMT3A not as one, we constructed two brain-specific conditional knockout mice. Methods: Cortices were dissected from Dnmt1 conditional knockout (CKO), Dnmt3a CKO, and respective littermate control mice at 18 weeks. RNA was isolated from three biological replicates for each genotype using TRIzol (Invitrogen) extraction and isopropanol precipitation. RNA samples were resuspended in water and further purified with RNeasy columns with on-column DNase treatment (Qiagen). RNA purity was assessed by measuring the A260/A280 ratio using a NanoDrop and RNA quality checked using an Agilent 2100 Bioanalyzer (Agilent Technologies). Approximately 250 ng of total RNA per sample were used for library construction by the TruSeq RNA Sample Prep Kit (Illumina) and sequenced using the Illumina HiSeq 2500 instrument according to the manufacturer's instructions. Sequence reads were aligned to mouse genome assembly mm10 and quantified using Cufflinks. Results: Genes differentially expressed in CKO mice compared to littermate control mice, or the Dnmt1 CKO signature, including GSN (the genes with the largest number of connection in the subnetwork) and SOX10 (a key transcription factor of myelination), significantly overlaps with the subnetwork. Broadly, the Dnmt1 CKO signature is enriched for genes involved in GO biological processes immune response, lipid metabolism, endocytosis, glial cell differentiation, and nerve ensheatment, consistent with biological function of the subnetwork. Moreover, the Dnmt1 CKO mice show increased predilection to seizures, an incidence also increased in patients with AD (Amatniek et al, 2006) as well as juvenile form of HD (Cloud et al, 2012). In contrast, the Dnmt3a CKO signature does not overlap with the subnetwork (p=0.07) and is not enriched for any GO biological process. Conclusions: These results suggest the Dnmt1 regulates common genes related with AD and HD while Dnmt3a has little effect. All of the mice used in this study were handled in accordance with IACUC-approved protocols. Dnmt1flox/flox (Fan et al, 2001; Jackson-Grusby et al, 2001) and Dnmt3aflox/flox (Nguyen et al, 2007) mice were backcrossed onto a C57BL/6 background and crossed with Olig1-cre mice to generate Dnmt1 conditional knockout (Olig1cre/+;Dnmt1flox/flox) and littermate control (Olig1+/+;Dnmt1flox/flox) mice, and Dnmt3a conditional knockout (Olig1cre/+;Dnmt3aflox/flox) and littermate control (Olig1+/+;Dnmt3aflox/flox) mice.
2014-07-31 | E-GEOD-58261 | biostudies-arrayexpress
Project description:Purpose: The goal of this study is to identify genes and molecular pathways whose expression is altered in the livers of Gpr151 knock-out (KO) mice compared to Gpr151 wild-type (WT). Methods: Total RNA was isolated from livers of fasted (5h) 16-week-old male mice. Deep sequencing of RNA from three wild-type and three knock-out mice was done using the mRNA-Seq pipeline at Novogene. The sequence reads that passed quality filters were aligned to the mouse GRCm38.p6 genome using STAR 2.6.1d. Differential expression testing was conducted using DESeq2. Results: Using an optimized data analysis workflow, we mapped about 40 million sequence reads per sample to the mouse genome (build mm10) and identified 54,532 transcripts in the livers of Gpr151 WT and KO mice. RNA-seq data identified 79 transcripts which were significantly upregulated in KO (p-adj < 0.05, log2FoldChange>1) and 338 transcripts which were significantly downregulated (p-adj<0.05, log2FoldChange<-1) in KO. Conclusions: Our study represents the first detailed analysis of the liver transcriptome of Gpr151 KO mice.
2022-10-14 | GSE196535 | GEO
Project description:Identification of the all RNA species associated with DNMT1. Using a comparative genome-scale approach we identified and correlated the RNA species physically associated with DNMT1 and proximal to the annotated genes to the methylation status of the corresponding loci and expression levels of the respective genes. This comparative approach delineated the first -DNMT1 centered- 'epitranscriptome' map, a comprehensive map cross-referencing DNMT1-interacting transcripts to (i) DNA methylation and (ii) gene expression profile. Relationship between DNMT1-RNA interactions, DNA methylation and gene expression
2012-12-01 | E-GEOD-32162 | biostudies-arrayexpress
Project description:DNA methyltransferase I plays the central role in maintenance of CpG DNA methylation patterns across the genome and alteration of CpG methylation patterns is a frequent and significant occurrence across many cancers. Cancer cells carrying hypomorphic alleles of Dnmt1 have become important tools for understanding Dnmt1 function and CpG methylation. In this study, we analyse colorectal cancer cells with a homozygous deletion of exons 3 to 5 of Dnmt1, resulting in reduced Dnmt1 activity. Although this cell model has been widely used to study the epigenome, the effects of the Dnmt1 hypomorph on cell signalling pathways and the wider proteome are largely unknown. In this study, we perform the first quantitative proteomic analysis of this important cell model and identify multiple signalling pathways and processes that are significantly dysregulated in the hypomorph cells. In Dnmt1 hypomorph cells, we observed a clear and unexpected signature of increased Epithelial-to-Mesenchymal transition (EMT) markers as well as reduced expression and sub-cellular re-localization of Beta-Catenin. Expression of wild-type Dnmt1 in hypomorph cells or knock-down of wild-type Dnmt1 did not recapitulate or rescue the observed protein profiles in Dnmt1 hypomorph cells suggesting that hypomorphic Dnmt1 causes changes not solely attributable to Dnmt1 protein levels. In summary we present the first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells and identify redistribution of Dnmt1 and its interaction partner Beta-Catenin
2021-09-08 | PXD014632 | Pride
Project description:Background DNA methylation is an epigenetic mark that restricts chromatin accessibility and serves to modulate temporal and spatial gene expression during organogenesis. Dnmt1 is one of the most studied DNA methyltransferases, and it is primarily involved in preserving the DNA methylation pattern in cells undergoing mitotic division. While the role of Dnmt1 in the embryonic lung endoderm has been revealed, its role in expansion, maintence and differentiation of the embryonic lung mesoderm is mostly unknown. Here, we present the first evidence showing that Dnmt1 is necessary for the proper development of the embryonic lung mesoderm. By selectively deleting Dnmt1 in the embryonic lung mesoderm we found that Dnmt1 is critical for the development of embryonic vasculature and fully commitment of mesoderm towards the lung mesenchymal cell lineages. Results Dnmt1 deletion in the embryonic lung mesenchyme at the E7.5 stage led to a lethal phenotype which was characterized by bilateral lung hypoplasia, impaired lung branching morphogenesis, and widespread hemorrhages in the parenchyma. The genesis of the hemorrhages was likely a result of halted development of lung vasculature, specifically the ontogeny of pericytes, which was detected in the mutant lungs. However, despite the severe mesenchyme alteration, differentiation of the lung endoderm appeared normal. When Dnmt1 was deleted at later developmental periods (E13.5), the lung matured normally and mutant pups were viable, although reduced differentiation of Pdgfr- myofibroblasts and alveolar simplification were observed in all mutant animals as soon as 7 days after birth. Gene expression profiling studies revealed that deletion of Dnmt1 induced the ectopic expression of genes specific for testis, placenta, and ovary, such as Tex10.1, Tex19.1 and Pet2 which suggested a loss of commitment of the lung mesoderm toward the pulmonary cell lineages. Conclusions Taken together our findings have shown that dnmt1 expression in the mesenchyme of the developing lung is crucial for restricting the differentiation capacity of the pulmonary mesoderm and, thus, ensuring the adequate differentiation of vasculature cells and myofibroblasts in the fetal and postnatal lung.
2021-06-15 | GSE174747 | GEO