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Efficient processing of widespread R-loops through an endo- and exo-cleavage coupling mode prevents genome instability

GSE269749 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2026/01/08 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
12 samples: 2 × U2OS, REXO4-D386A mutant stable expression cell line with Doxycycline added, vs 2 × U2OS, REXO4-D386A mutant stable expression cell line without Doxycycline added, vs 2 × U2OS, RNaseH1-D210N mutant stable expression cell line with Doxycycline added, vs 2 × U2OS, RNaseH1-D210N mutant stable expression cell line without Doxycycline added,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
R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunityScience advances · 2026
Summary (written by the submitters)
Excessive accumulation of R-loops is thought to be one of the major causes of genome instability. Endonuclease RNaseH1 acts as a classic, common R-loop resolvase to prevent R-loop accumulation genome-widely, whether there is any exonuclease complementing and teaming up with RNaseH1 to more efficiently resolve genome-wide R-loops is worth investigation.
Read the full summary ↓
Here we identify an exonuclease REXO4, which collaborates with RNaseH1 endonuclease to more efficiently degrade R-loops in an “endo- and exo-cleavage coupling” manner. Specifically, among many members of DEDDh exonuclease family, REXO4 has the most significant effect on R-loop suppression. REXO4 directly degrades RNA strand in R-loop from the end or internal nick through its 3’-5’ exonuclease activity, and also stimulates RNaseH1 endonuclease activity. The genome-wide R-loop regions regulated by REXO4 highly overlap with those regulated by RNaseH1, and REXO4 overexpression counteracts genome-wide R-loop accumulation caused by RNaseH1 deficiency. Furthermore, REXO4-deficient tumors display elevated R-loop mutation burden, and tumor patient-derived mutations in REXO4 enzymatic region all impair R-loop cleavage activity. Interfering with REXO4 increases the sensitivity of tumor cells to alkylating and G4 stabilizing drugs. Therefore, our study proposes a model for highly efficient processing of genome-wide R-loops by endo- and exo-cleavage, which provides additional insights into understanding the link between R-loop associated genome instability and tumors.
Published in
R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity
Yang H, Nie C, Qin Y et al. · Science advances 2026 · PMID 41706852 · doi:10.1126/sciadv.aeb4937
This dataset
Open GSE269749 in finder → Find more human ChIP / ATAC / CUT&Tag 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 GSE269749_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 peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1123612 and SRA study SRP513699. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41706852) ↗
Study design
2 × U2OS, REXO4-D386A mutant stable expression cell line with Doxycycline added, vs 2 × U2OS, REXO4-D386A mutant stable expression cell line without Doxycycline added, vs 2 × U2OS, RNaseH1-D210N mutant stable expression cell line with Doxycycline added, vs 2 × U2OS, RNaseH1-D210N mutant stable expression cell line without Doxycycline added,

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 8 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
Datasets on a similar topic

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