GEO series

Targeted disruption of DNMT1, 3A and 3B in human embryonic stem cells [DNMT3A/3B DKO]

GSE63280 Homo sapiens (human) DNA methylation 8 samples Submitted 2015/03/30 Platform GPL11154

At a glance

DNA methylation · human · 8 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Samples: 8 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

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.

Read the full summary ↓

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.

This dataset

Open GSE63280 in finder → Find more human methylation datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE63280_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA267140 and SRA study SRP049784. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 25822089) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 8 more — browse all 8 samples with per-sample file links →

Datasets on a similar topic

GSE297847 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A. 42 samples shares dnmt3a, dnmt1
GSE297781 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A (histone ChIP-seq) 14 samples shares dnmt3a, dnmt1
GSE319745 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A (RNA-seq) 10 samples shares dnmt3a, dnmt1
GSE337276 DNA methylation maintenance by DNMT1 is essential for human trophoblast stem cell homeostasis and differentiation [RNA-seq] 15 samples shares dnmt1, stem
GSE308271 DNMT3A:R882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency [RNA-Seq] 14 samples shares dnmt3a, stem
GSE265797 The inflammatory micro-environment induced by targeted CNS radiotherapy is underpined by disruption of DNA methylation [RNA-seq] 25 samples shares disruption, targeted
GSE298208 Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inﬂammatory signaling and disruption of the histone H3.3 chromatin loading pathway [RNA-seq] 24 samples shares disruption, stem
GSE318414 Lipid metabolism dysregulation in solar lentigo: a multi-system-level analysis reveals membrane instability and energy homeostasis disruption 14 samples shares disruption, stem

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.