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Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity [Bisulfite-Seq]

ABSTRACT: Dnmt1 is a key methyltransferase involved in the maintenance of DNA methylation. To determine whether developmental defects induced by hypomorphic DNA 5-methylcytosine methyltransferase activity can be offset by increasing DNA replication time, we produced fish that were mutant for both dnmt1 and DNA polymerase epsilon (pole1) and compared their whole genome bisultite sequencing and gene expression profiles to WT ones. We further determine that the observed rescue effect by pole1 is specific to dnmt1 by comparing whole-genome bisulfite sequencing and gene expression profiles of mutants for the Methionine Adenosyltransferase 2A (mat2aa) and microchromosome 10 (mcm10)

ORGANISM(S): Danio rerio

PROVIDER: GSE181572 | GEO | 2023/11/24

REPOSITORIES: GEO

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Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity [RNA-Seq]

Project description:Dnmt1 is a key methyltransferase involved in the maintenance of DNA methylation. To determine whether developmental defects induced by hypomorphic DNA 5-methylcytosine methyltransferase activity can be offset by increasing DNA replication time, we produced fish that were mutant for both dnmt1 and DNA polymerase epsilon (pole1) and compared their whole genome bisultite sequencing and gene expression profiles to WT ones. We further determine that the observed rescue effect by pole1 is specific to dnmt1 by comparing whole-genome bisulfite sequencing and gene expression profiles of mutants for the Methionine Adenosyltransferase 2A (mat2aa) and microchromosome 10 (mcm10)

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Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity

Project description:Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity

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Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dys-regulation of Epithelial-Mesenchymal Transition and subcellular re-localization of Beta-Catenin

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

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Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity [Bisulfite-Seq]

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S-adenosylhomocysteine hydrolase participates in DNA methylation inheritance

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Protracted NP95 binding to hemimethylated DNA disrupts SETDB1-mediated proviral silencing [RNA-seq]

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Histone ubiquitination-methylation crosstalk involving UHRF1 and SUV39H1/2 reinforces heterochromatin states in response to DNA hypomethylation

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Protracted NP95 binding to hemimethylated DNA disrupts SETDB1-mediated proviral silencing [RNA-seq]

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