GEO series

Tumor hypoxia causes DNA hypermethylation by reducing TET activity (TAB-Seq)

GSE71402 Mus musculus (mouse) DNA methylation 13 samples Submitted 2016/09/01 Platform GPL17021

At a glance

DNA methylation · mouse · 13 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Mus musculus (mouse)
Samples: 13 samples: 4 × shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a PHD2+/+ mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a sFlk1-overexpressing mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a empty PRRL2-vector-overexpressing mouseGroups are read from the sample names, not from the paper. Check the list below.
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)

Hypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET gene expression, basal metabolism, HIF activity or nuclear reactive oxygen species, but directly depends on oxygen shortage.

Read the full summary ↓

Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro, while also in patients, gene promoters are markedly more methylated in hypoxic than normoxic tumors. Affected genes are frequently involved in DNA repair, cell cycle regulation, angiogenesis and metastasis, indicating cellular selection of hypermethylation events. Overall, up to 50% of the tumor-associated hypermethylation is ascribable to hypoxia across various cancer types. Accordingly, spontaneous murine breast tumors become hypermethylated when rendered hypoxic through vessel pruning, whereas vessel normalisation rescues this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation.

This dataset

Open GSE71402 in finder → Find more mouse 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 GSE71402_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 PRJNA291092 and SRA study SRP061652. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 27533040) ↗

Study design

4 × shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a PHD2+/+ mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a sFlk1-overexpressing mouse vs 3 × shallow TABseq on a PyMT-induced breast tumor from a empty PRRL2-vector-overexpressing mouse

Supports a between-group comparison across 13 samples.

How we read this: 4 replicated groups read from 13 sample titles; they account for 13 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM1833748 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/+ mouse 1 shallow TABseq on a PyM…
GSM1833749 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/+ mouse 2 shallow TABseq on a PyM…
GSM1833750 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/+ mouse 3 shallow TABseq on a PyM…
GSM1833751 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse 1 shallow TABseq on a PyM…
GSM1833752 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse 2 shallow TABseq on a PyM…
GSM1833753 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse 3 shallow TABseq on a PyM…
GSM1833754 shallow TABseq on a PyMT-induced breast tumor from a PHD2+/- mouse 4 shallow TABseq on a PyM…
GSM1833755 shallow TABseq on a PyMT-induced breast tumor from a sFlk1-overexpressing mouse 1 shallow TABseq on a PyM…
GSM1833756 shallow TABseq on a PyMT-induced breast tumor from a sFlk1-overexpressing mouse 2 shallow TABseq on a PyM…
GSM1833757 shallow TABseq on a PyMT-induced breast tumor from a sFlk1-overexpressing mouse 3 shallow TABseq on a PyM…
GSM1833758 shallow TABseq on a PyMT-induced breast tumor from a empty PRRL2-vector-overexpressing mouse 1 shallow TABseq on a PyM…
GSM1833759 shallow TABseq on a PyMT-induced breast tumor from a empty PRRL2-vector-overexpressing mouse 2 shallow TABseq on a PyM…
GSM1833760 shallow TABseq on a PyMT-induced breast tumor from a empty PRRL2-vector-overexpressing mouse 3 shallow TABseq on a PyM…

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GSE245251 Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function [RNA-Seq] 24 samples shares activity, causes
GSE314221 Reducing CETP activity prevents memory decline in an Alzheimer’s disease mouse model. 16 samples shares reducing, activity
GSE247970 Cell of origin epigenetic priming determines susceptibility to Tet2 oncogenic mutation 76 samples shares tet
GSE272970 Bulk liver RNA-sequencing of mice co-exposed to simvastatin and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 60 samples shares tet
GSE254121 Time-Course Analysis of Hepatic Single-Nuclei RNA-Sequencing in Mice Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) 42 samples shares tet
GSE248933 Transcriptomic and epigenomic profiling of Tet TKO neural stem cells to study NSC specification and multipotency 36 samples shares tet

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