De novo DNA methyltransferases DNMT3A and DNMT3B are essential of global DNA methylation maintenance [RNA-Seq]
Transcriptomics Dataset
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General Information
AccessionGSE70721
TitleDe novo DNA methyltransferases DNMT3A and DNMT3B are essential of global DNA methylation maintenance [RNA-Seq]
DescriptionDNA methylation is the net result of deposition by DNA methyltransferases (DNMT1, 3A and 3B) and removal by the Ten-Eleven Translocation 1-3 (TET1-3) family of proteins and/or passive loss by replication. The relative contribution of the individual enzymes and pathways is only partially understood. Here we comprehensively analyzed and mathematically simulated the dynamics of DNA de-methylation during the reprogramming of the hypermethylated serum-cultured mouse embryonic stem cells (ESCs) to the hypomethylated 2i-cultured ground state of mESC. We show that DNA demethylation readily occurs in TET[1-/-, 2-/-] ESCs with similar kinetics as their WT littermates. Vitamin C activation of TET causes accelerated and more profound DNA demethylation without markedly affecting reprogramming kinetics. We developed a mathematical model that highly accurately predicts the global level of 5methyl- and 5hydroxymethylcytosine during the transition. Modeling and experimental validation show that the concentration of DNMT3A and DNMT3B determines the steady state level of global DNA methylation and absence of DNMT3A/B even in continued presence of DNMT1 results in gradual loss of 5mC. Taken together, DNMT1 alone is insufficient to maintain DNA methylation but requires the action of DNMT3A/3B that act as a dimmer switches.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70721
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Canned Analyses generated with the dataset

Dataset Accession
Tool Name

Interactive heatmap visualization of RNA-seq dataset GSE70721
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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