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Mithramycin Alters EWS::FLI1 DNA Binding and RNA Polymerase II Processivity to Inhibit Nascent Transcription [CUT&Tag]

GSE316977 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2026/01/22 Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 16 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
16 samples: 3 × TC32-FLI1-Media-72hr-biol vs 3 × TC32-FLI1-MMA-20nM-72hr-biol vs 3 × TC32-FLI1-MMA-100nM-18hr-biol vs 2 × TC32-FLI1-Media-18hr-biolGroups 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
Mithramycin alters EWS::FLI1 DNA binding and RNA polymerase II processivity to inhibit nascent transcriptionNature communications · 2026
Summary (written by the submitters)
Although many DNA binding natural products exert their effects through non-specific mechanisms, a therapeutic opportunity exists for a subset of these compounds that alter the expression or activity of specific driver oncogenes in specific cell contexts. In this study, we integrate CUT&Tag with Global Run-On Sequencing (CUT, Tag, and GRO) to show that the minor groove binding compound, mithramycin (MMA), inhibits the Ewing sarcoma oncogenic driver, the EWS::FLI1 transcription factor.
Read the full summary ↓
MMA causes either an increase or decrease in EWS::FLI1 binding to chromatin at downstream target response elements to poison nascent transcription. The reversal of EWS::FLI1 activity is limited by non-specific effects of the drug on RNAPII processivity but can be optimized by continuous administration at low concentration to cause more precise reversal of the oncogenic transcriptome and striking Ewing sarcoma xenograft regressions. The activity in vivo is further improved with a less-toxic second-generation analog, AIT-102.
Published in
Mithramycin alters EWS::FLI1 DNA binding and RNA polymerase II processivity to inhibit nascent transcription
Kaufman R, Flores G, Boguslawski EA et al. · Nature communications 2026 · PMID 41698909 · doi:10.1038/s41467-026-69488-9
This dataset
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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 GSE316977_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 PRJNA1405628 and SRA study SRP664771. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41698909) ↗
Study design
3 × TC32-FLI1-Media-72hr-biol vs 3 × TC32-FLI1-MMA-20nM-72hr-biol vs 3 × TC32-FLI1-MMA-100nM-18hr-biol vs 2 × TC32-FLI1-Media-18hr-biol

Supports a between-group comparison across 11 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 11 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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