GEO series

Inhibiting EZH2 Targets Atypical Teratoid Rhabdoid Tumor by Triggering Viral Mimicry via Both RNA and DNA Sensing Pathways [CUT&RUN]

GSE213248 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2024/09/05 Platform GPL18573

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 24 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: 24 samples: 8 conditions, mostly in triplicateGroups 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: Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathwaysNature communications · 2024

Summary (written by the submitters)

Loss of function mutations in SMARCB1 are prevalent in pediatric atypical teratoid rhabdoid tumors (ATRTs) and confer an oncogenic dependency on EZH2, providing a compelling rationale for treating these genetically defined cancers via EZH2 inhibition (EZH2i). EZH2i results in tumor regression in SMARCB1-deficient tumors in preclinical studies, but the molecular mechanism has not been fully elucidated.

Read the full summary ↓

Here we found that the sensitivity of SMARCB1-deficient tumors to EZH2i is associated with the viral mimicry response that depends on both double-stranded RNA (dsRNA) and cytoplasmic DNA sensing pathways. Unlike other epigenetic therapies targeting transcriptional repressors, viral mimicry by EZH2i in SMARCB1-deficient tumors is not triggered by crypt initiation of endogenous retroelements, but rather mediated by increased expression of genes enriched for intronic inverted-repeat Alu (IR-Alu) elements. Interestingly, we found that interferon-stimulated genes (ISGs) are highly enriched for dsRNA-forming intronic IR-Alu elements, suggesting a positive feedback loop whereby interferon response leads to dsRNA formation from intronic ISGs and activation of viral mimicry. Moreover, EZH2i in ATRT cells also enhances the expression of full-length LINE-1 elements, leading to genomic instability and cGAS/STING response in a process dependent on reverse transcriptase activity. Supporting this mechanism, co-depletion of dsRNA sensing and cytoplasmic DNA sensing completely rescues the viral mimicry response to EZH2i in SMARCB1-deficient tumors.

Published in

Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathways

Feng S, Marhon SA, Sokolowski DJ et al. · Nature communications 2024 · PMID 39472584 · doi:10.1038/s41467-024-53515-8

This dataset

Open GSE213248 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 GSE213248_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 PRJNA880265 and SRA study SRP396904. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39472584) ↗

Study design

8 conditions, mostly in triplicate

H3K27me3,UNC1999,Day4, ×3 H3K27me3,UNC1999,Day6, ×3 H3K27me3,UNC2400,Day4, ×3 H3K27me3,UNC2400,Day6, ×3 H3K4me3,UNC1999,Day4, ×3 H3K4me3,UNC1999,Day6, ×3 H3K4me3,UNC2400,Day4, ×3 H3K4me3,UNC2400,Day6, ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 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

GSM6576499 H3K27me3,UNC1999,Day4,Rep1 H3K27me3,UNC1999,Day4,
GSM6576500 H3K27me3,UNC1999,Day4,Rep2 H3K27me3,UNC1999,Day4,
GSM6576501 H3K27me3,UNC1999,Day4,Rep3 H3K27me3,UNC1999,Day4,
GSM6576502 H3K27me3,UNC1999,Day6,Rep1 H3K27me3,UNC1999,Day6,
GSM6576503 H3K27me3,UNC1999,Day6,Rep2 H3K27me3,UNC1999,Day6,
GSM6576504 H3K27me3,UNC1999,Day6,Rep3 H3K27me3,UNC1999,Day6,
GSM6576505 H3K27me3,UNC2400,Day4,Rep1 H3K27me3,UNC2400,Day4,
GSM6576506 H3K27me3,UNC2400,Day4,Rep2 H3K27me3,UNC2400,Day4,
GSM6576507 H3K27me3,UNC2400,Day4,Rep3 H3K27me3,UNC2400,Day4,
GSM6576508 H3K27me3,UNC2400,Day6,Rep1 H3K27me3,UNC2400,Day6,
GSM6576509 H3K27me3,UNC2400,Day6,Rep2 H3K27me3,UNC2400,Day6,
GSM6576510 H3K27me3,UNC2400,Day6,Rep3 H3K27me3,UNC2400,Day6,
GSM6576511 H3K4me3,UNC1999,Day4,Rep1 H3K4me3,UNC1999,Day4,
GSM6576512 H3K4me3,UNC1999,Day4,Rep2 H3K4me3,UNC1999,Day4,
GSM6576513 H3K4me3,UNC1999,Day4,Rep3 H3K4me3,UNC1999,Day4,
GSM6576514 H3K4me3,UNC1999,Day6,Rep1 H3K4me3,UNC1999,Day6,
GSM6576515 H3K4me3,UNC1999,Day6,Rep2 H3K4me3,UNC1999,Day6,
GSM6576516 H3K4me3,UNC1999,Day6,Rep3 H3K4me3,UNC1999,Day6,
GSM6576517 H3K4me3,UNC2400,Day4,Rep1 H3K4me3,UNC2400,Day4,
GSM6576518 H3K4me3,UNC2400,Day4,Rep2 H3K4me3,UNC2400,Day4,
GSM6576519 H3K4me3,UNC2400,Day4,Rep3 H3K4me3,UNC2400,Day4,
GSM6576520 H3K4me3,UNC2400,Day6,Rep1 H3K4me3,UNC2400,Day6,
GSM6576521 H3K4me3,UNC2400,Day6,Rep2 H3K4me3,UNC2400,Day6,
GSM6576522 H3K4me3,UNC2400,Day6,Rep3 H3K4me3,UNC2400,Day6,

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