Gene expression changes in mouse forebrain deficient in Dnmt1 and Dnmt3a
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19367 | GEO | 2010/12/03
SECONDARY ACCESSION(S): PRJNA120407
REPOSITORIES: GEO
Similar Datasets
Project description:Two major DNA methylation-catalyzing enzymes, Dnmt1 and Dnmt3a, are expressed in postmitotic neurons, but their function in the adult central nervous system is unclear. We generated conditional mutant mice (CamKIIa Cre; Dnmt loxP) that lack either Dnmt1 or Dnmt3a, or both, exclusively in forebrain excitatory neurons and found only double-knockout (DKO) mice exhibited abnormal hippocampal CA1 long-term plasticity and deficits of learning and memory. DKO neurons also exhibit a significant up-regulation of immune genes, such as class I MHC and Stat1, which are implicated in synaptic plasticity. Four pairs of 2-3 month-old DKO and litter mate control were used. RNA samples were extracted from the cortex and hippocampus for gene expression array analysis.
2010-12-03 | E-GEOD-19367 | biostudies-arrayexpress
Project description:DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Somatic patterns of DNA methylation are largely static, apart from focal dynamics at gene regulatory elements. To further advance our understanding of the role of DNA methylation in human development and disease, we inactivated all three catalytically active DNA methyltransferases in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing. Disruption of DNMT3A or DNMT3B individually, as well as of both enzymes in tandem, creates viable, pluripotent cell lines with distinct effects on their DNA methylation landscape as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome the immediate lethality, we generated a doxycycline (DOX) responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1 mutant lines. However, DOX-mediated repression of the exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death, demonstrating that DNA methylation is essential for human ESCs cultured in standard conditions. In summary, our data provide a comprehensive characterization of DNMT mutant ESCs, including single base genome-wide maps of their targets. RRBS methylation profiling of DNMT3A/3B DKO human ES cells
2015-03-30 | E-GEOD-63280 | biostudies-arrayexpress
Project description:DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Somatic patterns of DNA methylation are largely static, apart from focal dynamics at gene regulatory elements. To further advance our understanding of the role of DNA methylation in human development and disease, we inactivated all three catalytically active DNA methyltransferases in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing. Disruption of DNMT3A or DNMT3B individually, as well as of both enzymes in tandem, creates viable, pluripotent cell lines with distinct effects on their DNA methylation landscape as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome the immediate lethality, we generated a doxycycline (DOX) responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1 mutant lines. However, DOX-mediated repression of the exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death, demonstrating that DNA methylation is essential for human ESCs cultured in standard conditions. In summary, our data provide a comprehensive characterization of DNMT mutant ESCs, including single base genome-wide maps of their targets. RRBS methylation profiling of a time course of DNMT1* withdrawal in human ES cells
2015-03-30 | E-GEOD-63279 | biostudies-arrayexpress
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. RNA-seq performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines
2016-08-02 | E-GEOD-77003 | biostudies-arrayexpress
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. Reduced representation bisulfite sequencing (RRBS) performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines.
2016-08-02 | E-GEOD-84103 | biostudies-arrayexpress
Project description:DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Somatic patterns of DNA methylation are largely static, apart from focal dynamics at gene regulatory elements. To further advance our understanding of the role of DNA methylation in human development and disease, we inactivated all three catalytically active DNA methyltransferases in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing. Disruption of DNMT3A or DNMT3B individually, as well as of both enzymes in tandem, creates viable, pluripotent cell lines with distinct effects on their DNA methylation landscape as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome the immediate lethality, we generated a doxycycline (DOX) responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1 mutant lines. However, DOX-mediated repression of the exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death, demonstrating that DNA methylation is essential for human ESCs cultured in standard conditions. In summary, our data provide a comprehensive characterization of DNMT mutant ESCs, including single base genome-wide maps of their targets.
2015-03-30 | GSE63279 | GEO
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. Histone ChIP-seq of H3K4me3, H3K27me3, H3K4me1, and H3K27ac were performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines
2016-08-02 | E-GEOD-77002 | biostudies-arrayexpress
Project description:We generated base-resolution DNA methylomes of a series of DNMT knockout (KO) ES cells with improved coverage at highly repetitive elements. We find that DNMT1- and DNMT3a/3b-dependent activities actually work complementarily and simultaneously to establish symmetric CG methylation and CHH (H=A, T or C) methylation, and unexpectedly have “division of labor” to suppress retrotransposon long terminal repeats (LTRs) and long interspersed elements (LINEs), respectively. Our data also reveal CG density number of 30 seems like a 'threshold' to predetermine the level of methylation in wild type cells and the magnitude of methylation reduction in KO cells. Only genes with low CG number are either induced or surprisingly suppressed in hypomethylated genome. Our data unveil the concerted action of DNMT enzymes in the establishment/maintenance of methylation patterns. Genomic DNA from four different cell lines were treated with bisulfite and sequenced with the Illumina HiSeq platform using paired end reads.
2015-05-27 | E-GEOD-61457 | biostudies-arrayexpress
Project description:Here, we first establish an easy Multi-Stop system to simultaneously inactivate genes involved in DNA methylation and demethylation in zygotes through introduction of the stop codon by hA3A-eBE-Y130F-mediated base editor (BE). While Multi-Stop-derived Dnmt-null embryos display embryonic lethal due to gastrulation failure. Moreover, mutation combinations between Tet and Dnmt families show severe embryonic lethal and Dnmt1 or Dnmt3a/3b is indispensable for mouse gastrulation. Then WGBS and RNA-seq analysis of different mutant embryos reveals genes jointly maintained by Dnmt1 and Dnmt3a/3b that are critical for gastrulation.
2023-04-23 | GSE162903 | GEO
Project description:Dicer initiates RNA interference by generating small RNAs involved in various silencing pathways. Dicer participates in centromeric silencing, but its role in the epigenetic regulation of other chromatin domains has not been explored. Here we show that Dicer1 deficiency in Mus musculus leads to decreased DNA methylation, concomitant with increased telomere recombination and telomere elongation. These DNA-methylation defects correlate with decreased expression of Dnmt1, Dnmt3a and Dnmt3b DNA methyltransferases (Dnmts), and methylation levels can be recovered by their overexpression. We identify the retinoblastoma-like 2 protein (Rbl2) as responsible for decreased Dnmt expression in Dicer1-null cells, suggesting the existence of Dicer-dependent small RNAs that target Rbl2. We identify the miR-290 cluster as being downregulated in Dicer1-deficient cells and show that it silences Rbl2, thereby controlling Dnmt expression. These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis. Experiment Overall Design: Two-condition experiments. 6 comparisons. One dye-swap technical replicate for all samples. 2-color platform.
2008-06-19 | E-GEOD-11229 | biostudies-arrayexpress