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The SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma [RNA-Seq]

GSE211354 Homo sapiens (human) RNA-seq (gene expression) 54 samples Submitted 2024/04/19 Platform GPL24676Platform GPL21290
At a glance

RNA-seq (gene expression) · human · 54 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
54 samples: 18 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
The KAT module of the SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastomaScience advances · 2024
Summary (written by the submitters)
Pediatric cancers are frequently driven by fusion or amplification events that result in aberrant transcription factor activity. As transcription factors themselves remain challenging to target, an emerging therapeutic approach for these cancers is to target epigenetic complexes that help maintain oncogenic transcriptional programs. It is therefore critical to identify the complete set of epigenetic modulators maintaining the oncogenic epigenetic landscape of pediatric cancers.
Read the full summary ↓
Here, we used functional genomic screens to identify epigenetic complexes critical for viability in cell line models of MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We identified multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies in MYCN-amplified neuroblastoma. Integrating ChIP-seq, ATAC-seq, and RNA-seq with targeted protein-degradation and gene editing tools, we characterized the DNA recruitment sites of the SAGA complex in neuroblastoma, and the consequences of SAGA complex lysine acetyltransferase (KAT) activity loss on histone acetylation and gene expression. We demonstrate that loss of SAGA KAT activity suppresses MYC and MYCN gene expression programs and impairs cell cycle progression. Further, we showed that the SAGA complex is pharmacologically targetable with a KAT2A/KAT2B proteolysis targeting chimera molecule that demonstrated significant activity in vitro and in vivo. Our findings expand our understanding of the histone modifying complexes that maintain the oncogenic transcriptional state in this disease and suggest therapeutic potential for inhibitors of SAGA KAT activity in MYCN-amplified neuroblastoma.
Published in
The KAT module of the SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma
Malone CF, Mabe NW, Forman AB et al. · Science advances 2024 · PMID 38820154 · doi:10.1126/sciadv.adm9449
This dataset
Open GSE211354 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 GSE211354_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA869946 and SRA study SRP392482. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38820154) ↗
Study design
18 conditions, mostly in triplicate
KELLY cells, DMSO, 6 hours, ×3 KELLY cells, dTAG v1 TADA2B, 6 hours, ×3 KELLY cells, DMSO, 24 hours, ×3 KELLY cells, dTAG v1 TADA2B, 24 hours, ×3 KELLY cells, DMSO, 72 hours, ×3 KELLY cells, dTAG v1 TADA2B, 72 hours, ×3 KELLY cells, CRISPR LACZ, 7 days, ×3 KELLY cells, CRISPR sg2 TADA2B, 7 days, ×3 +10 more

Supports a between-group comparison across 54 samples.

How we read this: 18 replicated groups read from 54 sample titles; they account for 54 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

+ 14 more — browse all 54 samples with per-sample file links →

Datasets on a similar topic

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.