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C9orf72 Hexanucleotide Repeat RNA Drives Transcriptional Dysregulation Through Genome-wide Hybrid G-quadruplexes [ATAC-Seq]

GSE310926 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 10 samples Submitted 2026/02/24 Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 10 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
10 samples: 3 × C9-ALS, iMNs, line vs 2 × CTRL, iMNs, line 4, vs 2 × C9-ALS, iMNs, line 1, vs 2 × Isogenic CTRL, iMNs,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
C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexesNeuron · 2026
Summary (written by the submitters)
A hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. While repeat RNAs are implicated in disease pathogenesis, their mechanisms of actions remain incompletely understood. Here we show that GGGGCC repeat RNA engages chromatin genome-wide preferentially at promoter regions in patient cells.
Read the full summary ↓
This interaction obstructs RNA polymerase II and transcription factors with GC-rich motifs, leading to broad transcriptional repression. Biochemical assays, single-molecule imaging, and native bisulfite sequencing analyses demonstrate that GGGGCC repeat RNA intrinsically forms DNA:RNA hybrid G-quadruplexes with cognate DNA, providing a structural basis for transcriptional interference. Stabilization of these G-quadruplex structures exacerbates neuronal vulnerability to metabolic stress in patient-derived motor neurons and cortical organoids, whereas restoring key gene dysregulation improves neuronal resistance to stress. These findings uncover a previously unrecognized trans-acting mechanism whereby repetitive RNAs form hybrid structures with genomic DNA, disrupt gene regulation, and contribute to neurodegeneration.
Published in
C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes
Liu H, Liu M, Liu Y et al. · Neuron 2026 · PMID 41643661 · doi:10.1016/j.neuron.2025.12.005
This dataset
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.

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 GSE310926_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1367545 and SRA study SRP647524. Searching any of these in the dataset finder brings you back here.

Study design
3 × C9-ALS, iMNs, line vs 2 × CTRL, iMNs, line 4, vs 2 × C9-ALS, iMNs, line 1, vs 2 × Isogenic CTRL, iMNs,

Supports a between-group comparison across 9 samples.

How we read this: 4 replicated groups read from 10 sample titles; they account for 9 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
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