GEO series
The SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma [ChIP-Seq]
GSE211953
Homo sapiens (human)
ChIP-seq / ATAC-seq (genome binding and open chromatin)
35 samples
Submitted 2024/04/19
Platform GPL24676
At a glance
ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 35 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
- 35 samples: 28 distinct titles, 7 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.
- 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
Malone CF, Mabe NW, Forman AB et al.
· Science advances 2024
· PMID 38820154
· doi:10.1126/sciadv.adm9449
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 GSE211953_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 PRJNA873048 and SRA study SRP394292. Searching any of these in the dataset finder brings you back here.
Study design
28 distinct titles, 7 of them repeated
PROTAC experiment, KELLY cells, DMSO, H3K27ac… ×2
PROTAC experiment, KELLY cells, DMSO, H3K9ac … ×2
PROTAC experiment, KELLY cells, DMSO, Input, … ×2
PROTAC experiment, KELLY cells, GSK6991, H3K2… ×2
PROTAC experiment, KELLY cells, GSK6991, H3K9… ×2
PROTAC experiment, KELLY cells, GSK6991, Inpu… ×2
PROTAC experiment, KELLY cells, GSK6991, MYCN… ×2
How we read this: Read from 35 sample titles: 28 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
- GSM6506050 KELLY-TADA2Bdeg cells, DMSO, HA antibody, 6 hours
- GSM6506051 KELLY-TADA2Bdeg cells, DMSO, Input, 6 hours
- GSM6506052 KELLY-TADA2Bdeg cells, dTAGv1, HA antibody, 6 hours
- GSM6506053 KELLY-TADA2Bdeg cells, dTAGv1, Input, 6 hours
- GSM6506054 NB1-TADA2Bdeg cells, DMSO, HA antibody, 6 hours
- GSM6506055 NB1-TADA2Bdeg cells, DMSO, Input, 6 hours
- GSM6506056 NB1-TADA2Bdeg cells, dTAGv1, HA antibody, 6 hours
- GSM6506057 NB1-TADA2Bdeg cells, dTAGv1, Input, 6 hours
- GSM6506058 NGP-TADA2Bdeg cells, DMSO, HA antibody, 6 hours
- GSM6506059 NGP-TADA2Bdeg cells, DMSO, Input, 6 hours
- GSM6506060 NGP-TADA2Bdeg cells, dTAGv1, HA antibody, 6 hours
- GSM6506061 NGP-TADA2Bdeg cells, dTAGv1, Input, 6 hours
- GSM6506062 KELLY cells, DMSO, H3K9ac antibody, 6 hours
- GSM6506063 KELLY cells, dTAGv1 TADA2B, H3K9ac antibody, 6 hours
- GSM6506066 KELLY cells, DMSO, H3K27ac antibody, 6 hours
- GSM6506067 KELLY cells, dTAGv1 TADA2B, H3K27ac antibody, 6 hours
- GSM6506070 KELLY cells, DMSO, MYCN antibody, 6 hours
- GSM6506071 KELLY cells, dTAGv1 TADA2B, MYCN antibody, 6 hours
- GSM6506074 KELLY cells, DMSO, Input, 6 hours
- GSM6506075 KELLY cells, dTAGv1 TADA2B, Input, 6 hours
- GSM7871847 PROTAC experiment, KELLY cells, DMSO, H3K27ac antibody, 6 hours, replicate 1
- GSM7871848 PROTAC experiment, KELLY cells, DMSO, H3K27ac antibody, 6 hours, replicate 2
- GSM7871849 PROTAC experiment, KELLY cells, DMSO, H3K9ac antibody, 6 hours, replicate 1
- GSM7871850 PROTAC experiment, KELLY cells, DMSO, H3K9ac antibody, 6 hours, replicate 2
- GSM7871851 PROTAC experiment, KELLY cells, DMSO, Input, 6 hours, replicate 1
- GSM7871852 PROTAC experiment, KELLY cells, DMSO, Input, 6 hours, replicate 2
- GSM7871853 PROTAC experiment, KELLY cells, DMSO, MYCN antibody, 6 hours, replicate 1
- GSM7871854 PROTAC experiment, KELLY cells, GSK6991, H3K27ac antibody, 6 hours, replicate 1
- GSM7871855 PROTAC experiment, KELLY cells, GSK6991, H3K27ac antibody, 6 hours, replicate 2
- GSM7871856 PROTAC experiment, KELLY cells, GSK6991, H3K9ac antibody, 6 hours, replicate 1
- GSM7871857 PROTAC experiment, KELLY cells, GSK6991, H3K9ac antibody, 6 hours, replicate 2
- GSM7871858 PROTAC experiment, KELLY cells, GSK6991, Input, 6 hours, replicate 1
- GSM7871859 PROTAC experiment, KELLY cells, GSK6991, Input, 6 hours, replicate 2
- GSM7871860 PROTAC experiment, KELLY cells, GSK6991, MYCN antibody, 6 hours, replicate 1
- GSM7871861 PROTAC experiment, KELLY cells, GSK6991, MYCN antibody, 6 hours, replicate 2
Datasets on a similar topic
- GSE211354 The SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma [RNA-Seq] 54 samples shares saga, mycn-amplified, neuroblastoma, maintains, oncogenic, complex, program
- GSE262886 The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma [CUT&RUN] 10 samples shares saga, oncogenic, program
- GSE317235 SAGA/ATAC complexes sustain aberrant chromatin regulation and metabolic programs in diffuse midline glioma 18 samples shares saga, complex, program
- GSE256316 SWI/SNF complex-mediated ZNF410 cooperative binding maintains chromatin accessibility and enhancer activity [ChIP-Seq] 121 samples shares maintains, chip-seq, complex
- GSE294307 5-hydroxymethylcytosine deposition mediates Polycomb Repressive Complex 2 function in MYCN-amplified neuroblastoma [CUT&Run] 18 samples shares mycn-amplified, neuroblastoma, complex
- GSE314543 Lamin A/C maintains genome topology and regulates transcriptional programs essential for virus-driven B cell activation [ChiP-seq] 16 samples shares maintains, chip-seq, program
- GSE164456 Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma 69 samples shares mycn-amplified, neuroblastoma, program
- GSE294526 The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma [RNA-seq II] 21 samples shares neuroblastoma, oncogenic, complex
Share this dataset
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