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Targeting the CHD3 Chromatin Remodeler Exploits a Synthetic Lethal Vulnerability in SWI/SNF-Deficient Cancers via Toxic Derepression of PARD3B

GSE323137 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 39 samples Submitted 2026/05/21 Platform GPL24676Platform GPL28038
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 39 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
39 samples: 37 distinct titles, 2 of them repeatedGroups 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)
SWI/SNF-deficient cancers characterized by dual SMARCA4/SMARCA2 loss, including undifferentiated thoracic sarcomas and subsets of lung adenocarcinoma, represent a major therapeutic challenge. While paralog-targeting strategies exist for single-subunit loss, dual-deficient tumors lack actionable targets. Here, we identify the CHD3/NuRD nucleosome remodeling complex as a critical synthetic lethal vulnerability in these malignancies.
Read the full summary ↓
Through an integrated genomic analysis, we demonstrate that in the absence of SWI/SNF, CHD3 acts as an essential "epigenetic brake" at the enhancer of the cell polarity regulator PARD3B. Loss of CHD3 triggers aberrant chromatin hyper-accessibility and toxic derepression of PARD3B. We further elucidate that PARD3B accumulation drives cell death by inducing the "functional uncoupling" of MYC signaling. This occurs via spatial perturbation of upstream signaling hubs, which silences MYC transcriptional output without degrading the protein itself. Therapeutically, CHD3 depletion led to robust tumor regression in SWI/SNF-deficient xenografts, validating the mechanism of PARD3B upregulation and the collapse of the MYC pathway in vivo. Our study defines a novel mode of synthetic lethality driven by "gain-of-toxicity" rather than loss of survival signals, uncovering a fatal cross-complex dependency. We propose that targeting CHD3 to unleash PARD3B toxicity offers a promising therapeutic avenue for treatment-refractory SWI/SNF-deficient cancers.
This dataset
Open GSE323137 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 GSE323137_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 PRJNA1432056 and SRA study SRP681009. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
37 distinct titles, 2 of them repeated
RNAseq_H23_Mock_96h ×2 RNAseq_H23_PARD3B_96h ×2

How we read this: Read from 39 sample titles: 37 distinct titles with little repetition. 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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