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A potent and selective small-molecule degrader of ENL suppresses leukemia progression in vivo (ChIP-Seq)

GSE245925 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 63 samples Submitted 2024/09/13 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 63 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
63 samples: 20 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
A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progressionScience advances · 2024
Summary (written by the submitters)
ENL, a stoichiometric component of the Super Elongation Complex (SEC) as well as the histone H3K79 methyltransferase DOT1L complex, is involved in the regulation of transcription elongation. Loss-of-function studies of ENL highlighted an essential role for its chromatin reader YEATS domain in the progression of acute leukemia, suggesting ENL as an attractive therapeutic target for leukemia therapy.
Read the full summary ↓
Proteolysis targeting chimeras (PROTACs), a class of new therapeutic modalities, have the potential to degrade target proteinsthrough the ubiquitin-proteasome system. PROTACs have the potential to deliver robust therapeutic effects at low doses and infrequent dosing regimens with less side-effects. Here, we designed and synthesized a serial of ENL PROTACs. Through screening by ENL degradation in human leukemia cells, we identified MS47 as a potent ENL PROTAC. MS47 efficiently and specifically degrades ENL in a concentration-dependent and time dependent manner. In line with the mechanism of action of PROTACs, proteasome inhibitors can block ENL degradation mediated by MS47. MS47 suppresses survival and growth of a panel of acute leukemia cells, and efficiently suppresses the expression of ENL target genes, including Hoxa9, Meis1, Myb and Myc. In disseminated xenograft model, MS47 significantly benefits mouse survival, inhibits leukemia cell growth in vivo. No obvious toxic effect shown in toxicity test in vivo. Modest changes occurred on normal hematopoiesis. Together, our study developed a potent ENL PROTAC for leukemia treatment.
Published in
A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression
Xue Z, Qin L, Xuan H et al. · Science advances 2024 · PMID 39196923 · doi:10.1126/sciadv.ado1432
This dataset
Open GSE245925 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 GSE245925_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 PRJNA1030399 and SRA study SRP467592. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39196923) ↗
Study design
20 conditions, mostly in triplicate
MV411 DMSO 24h DOT1L MNase ×3 MV411 DMSO 24h H3K79me2 soni ×3 MV411 DMSO 6h AFF1 MNase ×3 MV411 DMSO 6h CDK9 DSG ×3 MV411 DMSO 6h DOT1L MNase ×3 MV411 DMSO 6h ENL soni ×3 MV411 DMSO 6h Pol2S2P MNase ×3 MV411 DMSO 6h Pol2 MNase ×3 +15 more

Supports a between-group comparison across 60 samples.

How we read this: 20 replicated groups read from 63 sample titles; they account for 60 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

+ 23 more — browse all 63 samples with per-sample file links →

Datasets on a similar topic

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

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