Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA191566 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:mRNA-seq in DNA methylation deficient mouse embryonic fibroblasts
| PRJNA191560 | ENA
Project description:The E3 ligase UHRF1 is an essential epigenetic cofactor for DNMT1 dependent maintenance DNA methylation, which provides a binding platform for DNMT1 by both cooperative binding of histones and hemi-methylated DNA as well as by ubiquitinating histone H3. Here, we conduct a comprehensive screen to identify novel ubiquitination targets of UHRF1 and its paralogue UHRF2 by comparing the ubiquitome of wildtype (wt), UHRF1- and UHRF2-deficient mouse embryonic stem cells. With an antibody-dependent enrichment of ubiquitin remnant motif-containing peptides followed by isobaric-labeling based quantitative mass spectrometry, we find both known and novel E3 ligase substrates of UHRF1 involved in a variety of biological processes such as RNA processing, DNA methylation and DNA damage repair.
2017-10-24 | PXD006593 | Pride
Project description:DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease. DNA methylation levels in Dnmt1+/+ mouse embryonic fibroblasts measured by HpaII tiny fragment Enrichment by Ligation-mediated PCR Sequencing (HELP-seq)
2013-03-01 | E-GEOD-44757 | biostudies-arrayexpress
Project description:DNA methylation plays a critical role in development, particularly in repressing retrotransposons. The mammalian methylation landscape is dependent on the combined activities of the canonical maintenance enzyme Dnmt1 and the de novo Dnmts, 3a and 3b. Here we demonstrate that Dnmt1 displays de novo methylation activity in vitro and in vivo with specific retrotransposon targeting. We used whole-genome bisulfite and long-read Nanopore sequencing in genetically engineered methylation depleted embryonic stem cells to provide an in-depth assessment and quantification of this activity. Utilizing additional knockout lines and molecular characterization, we show that Dnmt1's de novo methylation activity depends on Uhrf1 and its genomic recruitment overlaps with targets that enrich for Trim28 and H3K9 trimethylation. Our data demonstrate that Dnmt1 can de novo add and maintain DNA methylation, especially at retrotransposons and that this mechanism may provide additional stability for long-term repression and epigenetic propagation throughout development.
2021-06-29 | PXD025736 | Pride
Project description:Background: Global DNA methylation contributes to genomic integrity by supressing repeat associated transposition events. Several chromatin factors are required in addition to DNA methyltransferases to maintain DNA methylation at intergenic and satellite repeats. Embryos lacking Lsh, a member of the SNF2 superfamily of chromatin helicases, are hypomethylated. The interaction of Lsh with the de novo methyltransferase, Dnmt3b, facilitates the deposition of DNA methylation at stem cell genes. We wished to determine if a similar targeting mechanism operates to maintain DNA methylation at repetitive sequences. Results: We used HELP-seq to map genome wide DNA methylation patterns in Lsh-/- and Dnmt3b-/- somatic cells. DNA methylation is predominantly lost from specific genomic repeats in Lsh-/- cells: LTR-retrotransposons, LINE-1 repeats and mouse satellites. RNA-seq experiments demonstrate that specific IAP (Intracisternal A-type particle) LTRs and satellites, but not LINE-1 elements, are aberrantly transcribed inLsh-/- cells. LTR hypomethylation in Dnmt3b-/- cells is moderate and hypomethylated repetitive elements (IAP, LINE-1 and satellite) are silent. Chromatin immunoprecipitation (ChIP) indicates that repressed LINE-1 elements gain H3K4me3, but H3K9me3 levels are unaltered in Lsh-/- cells, indicating that DNA hypomethylation alone is not permissive for their transcriptional activation. Mis-expressed IAPs and satellites lose H3K9me3 and gain H3K4me3 in Lsh-/- cells. Conclusions: Our study emphasizes that regulation of repetitive elements by DNA methylation is selective and context dependent. We propose a model where Lsh is specifically required at a precise developmental window to target de novo methylation to repeat sequences, which is subsequently maintained by Dnmt1 in somatic cells to enforce repeat silencing thus contributing to genomic integrity. Two pairs of genomic samples compared: WT and Lsh-/- DNA isolations from tail-tip fibroblasts; WT and Dnmt3b knockout DNA isolations from mouse embryonic fibroblasts.
2013-12-09 | E-GEOD-52476 | biostudies-arrayexpress
Project description:Chip-seq for H3K27me3 and H3K4me3 in DNA methylation deficient mouse embryonic fibroblasts
| PRJNA189742 | ENA
Project description:DNMT1 maintains DNA methylation profile and regulates gene expression. Although DNMT1 interacts with other proteins that regulate gene expressions, it remains unclear how the protein-protein interaction or the catalytic activity of DNMT1 itself affect gene expression and DNA methylation pattern. In this study, immunofluorescence staining showed abnormal DNA methylation pattern in chromosome arms of DNMT1-deficient (1KO) mouse embryonic stem cells (ESCs), and we hypothesized that DNMT1 helps methylation activity of DNMT3. To validate this hypothesis, we generate transgenic 1KO ESCs expressing catalytic inactive DNMT1 (1KO+1CI). Here, we used RNA-seq to analyze the effect of catalytic-dependent or -independent DNMT1 activity on gene expression in ESCs or epiblast-like cells (EpiLCs) induction.
2022-01-01 | GSE179006 | GEO
Project description:Genome-wide DNA methylation maps of mouse embryonic fibroblasts and reprogramming cells modulated by cell cycle and Dnmt1 expression
| PRJNA359751 | ENA
Project description:DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease. comparison of Dnmt1+/+ vs Dnmt1-/- mouse embryonic fibroblasts by ChIP-seq for H3K27me3 and H3K4me3
2013-02-20 | E-GEOD-44393 | biostudies-arrayexpress
Project description:DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease. comparison of Dnmt1+/+ vs Dnmt1-/- mouse embryonic fibroblasts by strand-specific mRNA-seq
2013-03-01 | E-GEOD-44733 | biostudies-arrayexpress