GEO series

Nitric oxide inhibits ten-eleven translocation DNA demethylase activity to regulate 5mC and 5hmC across the genome [RNA-seq]

GSE248150 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/05/01 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 12 samples: 3 × MDA-MB-231, Control, 10 days, vs 3 × MDA-MB-231, DETA/NO, 10 days, vs 3 × MDA-MB-468, Control, 10 days, vs 3 × MDA-MB-468, DETA/NO, 10 days,Groups 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.
Paper: Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genomeResearch square · 2024

Summary (written by the submitters)

DNA methylation at cytosine bases of eukaryotic DNA (5-methylcytosine, 5mC) is a heritable epigenetic mark that can regulate gene expression in health and disease. Enzymes that metabolize 5mC have been well-characterized yet the discovery of endogenously produced signaling molecules that regulate DNA methyl-modifying machinery have not been described.

Read the full summary ↓

Herein, we report that the free radical signaling molecule nitric oxide (NO) can directly inhibit the Fe(II)/2-OG-dependent DNA demethylases ten-eleven translocation (TET) and Human AlkB homolog 2 (ALKBH2). Physiologic NO concentrations reversibly inhibited TET and ALKBH2 demethylase activity by binding to the mononuclear non-heme iron atom in place of O2 to form a dinitrosyliron complex (DNIC). In cancer cells treated with exogeneous NO, or cells endogenously synthesizing NO, there was a global increase in DNA 5mC, a substrate for TET, that could not be attributed to increased DNA methyltransferase activity. 5mC was also elevated in NO-producing mouse xenograft and patient derived xenograft tumors. Genome-wide DNA methylome analysis of cells chronically treated with NO (10 days) demonstrated enrichment of 5mC at gene-regulatory loci which correlated to the expression of NO-regulated tumor-associated genes. Regulation of DNA methylation is distinctly different from canonical NO-signaling and represents a novel epigenetic regulatory mechanism of NO.

Published in

Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome

Thomas D, Palczewski M, Kuschman H et al. · Research square 2024 · PMID 38645113 · doi:10.21203/rs.3.rs-4131804/v1

This dataset

Open GSE248150 in finder → Find more human RNA-seq 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 GSE248150_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1041834. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38645113) ↗

Study design

3 × MDA-MB-231, Control, 10 days, vs 3 × MDA-MB-231, DETA/NO, 10 days, vs 3 × MDA-MB-468, Control, 10 days, vs 3 × MDA-MB-468, DETA/NO, 10 days,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM7906436 MDA-MB-231, Control, 10 days, rep1 MDA-MB-231, Control, 10…
GSM7906437 MDA-MB-231, Control, 10 days, rep2 MDA-MB-231, Control, 10…
GSM7906438 MDA-MB-231, Control, 10 days, rep3 MDA-MB-231, Control, 10…
GSM7906439 MDA-MB-231, DETA/NO, 10 days, rep1 MDA-MB-231, DETA/NO, 10…
GSM7906440 MDA-MB-231, DETA/NO, 10 days, rep2 MDA-MB-231, DETA/NO, 10…
GSM7906441 MDA-MB-231, DETA/NO, 10 days, rep3 MDA-MB-231, DETA/NO, 10…
GSM7906442 MDA-MB-468, Control, 10 days, rep1 MDA-MB-468, Control, 10…
GSM7906443 MDA-MB-468, Control, 10 days, rep2 MDA-MB-468, Control, 10…
GSM7906444 MDA-MB-468, Control, 10 days, rep3 MDA-MB-468, Control, 10…
GSM7906445 MDA-MB-468, DETA/NO, 10 days, rep1 MDA-MB-468, DETA/NO, 10…
GSM7906446 MDA-MB-468, DETA/NO, 10 days, rep2 MDA-MB-468, DETA/NO, 10…
GSM7906447 MDA-MB-468, DETA/NO, 10 days, rep3 MDA-MB-468, DETA/NO, 10…

Datasets on a similar topic

GSE248151 Nitric oxide inhibits Ten-eleven translocation DNA demethylase activity to regulate 5mC and 5hmC across the genome 28 samples shares 5hmc, translocation, demethylase, ten-eleven, inhibits, activity, regulate
GSE300083 The Lysine Demethylase Kdm4C is an Oncogenic Driver and Regulates ERK Activity in KRAS Mutant Pancreatic Ductal Adenocarcinoma [RNA-Seq] 12 samples shares demethylase, activity, regulate, rna-seq
GSE236270 Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation [MDA-MB-231-RNASeq] 6 samples shares demethylase, inhibits, activity, regulate
GSE236269 Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation [MDA-MB-468-RNASeq] 6 samples shares demethylase, inhibits, activity, regulate
GSE236272 Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation 20 samples shares demethylase, inhibits, activity, regulate
GSE331257 Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states [RNA-Seq] 24 samples shares demethylase, inhibits, rna-seq
GSE300200 The Lysine Demethylase Kdm4C is an Oncogenic Driver and Regulates ERK Activity in KRAS Mutant Pancreatic Ductal Adenocarcinoma 26 samples shares demethylase, activity, regulate
GSE300199 The Lysine Demethylase Kdm4C is an Oncogenic Driver and Regulates ERK Activity in KRAS Mutant Pancreatic Ductal Adenocarcinoma [ChIP-seq] 14 samples shares demethylase, activity, regulate

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