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Targeting DCAF5 suppresses SMARCB1-mutant cancer via stabilizing SWI/SNF

GSE215022 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2024/03/22 Platform GPL24676
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
Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNFNature · 2024
Summary (written by the submitters)
While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and presents a conundrum for precision therapy because the proteins are no longer present. SMARCB1-mutant cancers epitomize this challenge because these highly lethal cancers are driven by inactivation of a single gene, a subunit of SWI/SNF chromatin remodeling complexes.
Read the full summary ↓
To generate mechanistic insight into the consequences of SMARCB1 mutation and to seek vulnerabilities, we contributed 16 SMARCB1-mutant cell lines to a near-genomewide CRISPR screen as part of the Cancer Dependency Map1-3. Here we report that the little-studied gene DCAF5 (DDB1-CUL4 Associated Factor 5) is a specific dependency in SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and in the absence of SMARCB1 DCAF5 causes degradation of incompletely assembled SWI/SNF complexes. Upon inhibition of DCAF5 SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore gene expression to levels sufficient to fully reverse the cancer state, including in a xenograft mouse model. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of DCAF5 may be sufficient to restore substantial SWI/SNF function and reverse cancer phenotypes caused by SMARCB1 loss.
Published in
Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF
Radko-Juettner S, Yue H, Myers JA et al. · Nature 2024 · PMID 38538798 · doi:10.1038/s41586-024-07250-1
This dataset
Open GSE215022 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 GSE215022_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 PRJNA888094 and SRA study SRP401521. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38538798) ↗
Study design
8 conditions, mostly in triplicate
G401_ATAC_shCTRL ×3 G401_ATAC_shDCAF5 ×3 G401_ATAC_shCTRL_DMSO ×3 G401_ATAC_shCTRL_BRM014 ×3 G401_ATAC_shDCAF5_DMSO ×3 ATAC_G401_dTAGDCAF5_DMSO_4h ×3 ATAC_G401_dTAGDCAF5_V1_4h ×3 G401_ATAC_shDCAF5_BRM014 ×2 +1 more

Supports a between-group comparison across 23 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 23 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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