Ontology highlight
ABSTRACT:
PROVIDER: PRJNA957711 | ENA |
REPOSITORIES: ENA
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Project description:Despite considerable speculation for the role of cytosine (DNA) methylation in biological and molecular processes in insects, direct functional tests are lacking. Here we provide evidence for the functional role of the maintenance DNA methyltransferase 1 (Dnmt1) in an insect using experimental manipulation. Through RNA interference (RNAi) we successfully post-transcriptionally knocked down Dnmt1 in ovarian tissue of the hemipteran Oncopeltus fasciatus (the large milkweed bug). Individuals depleted for dnmt1, and subsequently DNA methylation, failed to reproduce. Manipulating the levels of DNA methylation did not result in changes in overall gene expression. Furthermore, reductions in levels of DNA methylation at transposable elements (TEs) did not lead to large-scale reactivation of TE transcription. Despite the lack of a causal relationship between reduced DNA methylation and gene expression in the tissue we surveyed, eggs were inviable revealing an important function of DNA methylation in O. fasciatus. Our work provides direct experimental evidence for a functional role of Dnmt1 and DNA methylation in insects and presents O. fasciatus as a tractable model for further exploration of the function of DNA methylation in other tissues and life history circumstances for insects.
2018-07-05 | GSE109199 | GEO
Project description:This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. To determine DAXX binding sites in the prostate cancer (PCa) genome, the PC3 cell line was used. A stable DAXX shRNA knockdown (K/D) PC3 cell line and a control shRNA counterpart, were compared in a ChIP-Seq study.
2015-06-24 | E-GEOD-68647 | biostudies-arrayexpress
Project description:The maternal and early embryonic transcriptome of the milkweed bug Oncopeltus fasciatus
| PRJNA79671 | ENA
Project description:Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidence of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA-adenine methylase identification (DamID) method, we identified Dnmt1-binding regions in 4-cell and 8-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refute the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the long interspersed nuclear elements (LINE1) and endogenous retrovirus type-K (ERVK) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding-domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.
2020-07-19 | GSE150462 | GEO
Project description:Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidence of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA-adenine methylase identification (DamID) method, we identified Dnmt1-binding regions in 4-cell and 8-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refute the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the long interspersed nuclear elements (LINE1) and endogenous retrovirus type-K (ERVK) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding-domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.
2020-07-19 | GSE104437 | GEO
Project description:Previous study demonstrated that HDAC3 has a critical role in MM proliferation; however, the underlying mechanism has not yet been elucidated. We identify that HDAC3 inhibition targets DNMT1 through dual regulations. We demonstrate that knockdown of DNMT1 leads to apoptosis and significant growth inhibition in myeloma cells. HDAC3 inhibition by gene silencing or HDAC3 selective inhibitor BG45 downregulates an oncoprotein c-Myc through its acetylation. c-Myc directly regulates DNMT1 expression at its enhancer region. Furthermore, HDAC3 directly regulates the stability of DNMT1 protein through its acetylation. Pharmaceutical inhibition of HDAC3 and DNMT1 synergistically induce MM growth inhibition in in vitro and in vivo settings. The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of HDAC3 or DNMT1 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (MM.1S).
2017-06-01 | GSE86147 | GEO
Project description:This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX.
2015-06-24 | GSE68647 | GEO
Project description:Development of Primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of Embryonic Ectoderm Development (EED) and Histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created a conditional deletion in EED and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes. Integrating chromatin and whole genome bisulfite sequencing of epiblast and PGCs, we identified a poised repressive signature of H3K27me3/DNA methylation which we propose is established in the epiblast where EED and DNMT1 interact. Thus, EED joins DNMT1 in regulating the timing of sex-specific PGC differentiation during the critical window when the gonadal niche cells specialize into an ovary or testis.
2022-05-11 | GSE139413 | GEO