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TFE3 fusion oncoprotein condensates drive epigenetic reprogramming and cancer progression [CUT&RUN]

GSE281165 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 43 samples Submitted 2025/04/02 Platform GPL34281
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 43 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
43 samples: 6 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
TFE3 fusion oncoprotein condensates drive transcriptional reprogramming and cancer progression in translocation renal cell carcinomaCell reports · 2025
Summary (written by the submitters)
Translocation renal cell carcinoma (tRCC) presents a significant clinical challenge due to its aggressiveness and limited treatment options. This cancer is primarily driven by fusion oncoproteins (FOs) arising from chromosomal rearrangements, yet their role in oncogenesis remains incompletely understood. Here we investigate TFE3 fusion in tRCC, focusing on NONO::TFE3 and SFPQ::TFE3, constituting 30-40% of all TFE3 FOs.
Read the full summary ↓
We find that TFE3 FOs form liquid-like condensates with heightened transcriptional activity, selectively recruiting active transcription markers to TFE3 target genes and promoting cell proliferation, migration, and drug resistance. The coiled-coil domains (CCD) of NONO and SFPQ are essential for condensate formation, prolonging TFE3 FOs' chromatin binding time and enhancing transcription. We comprehensively investigated the genome-wide recruitment of TFE3 FOs and their CCD-altered variants, uncovering widespread changes in chromatin accessibility and genomic binding specifically at TFE3 and AP-1 regulated loci. We also observe altered H3K27ac deposition at enhancers and super-enhancers notably at pro-growth and stemness markers such as BCL2 and CD44, and identify novel oncogenic target genes of TFE3 FOs. Disruption of condensate formation, resulting from CCD domain alterations in FOs, robustly dysregulates their role in chromatin accessibility, chromatin binding, H3K27ac occupancy, and gene expression. Altogether our integrated analyses underscore the critical functions of TFE3 FO condensates in driving RCC progression, offering pivotal insights for future targeted therapeutic strategies.
Published in
TFE3 fusion oncoprotein condensates drive transcriptional reprogramming and cancer progression in translocation renal cell carcinoma
So CL, Lee YJ, Vokshi BH et al. · Cell reports 2025 · PMID 40222010 · doi:10.1016/j.celrep.2025.115539
This dataset
Open GSE281165 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 GSE281165_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 PRJNA1182651 and SRA study SRP543443. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40222010) ↗
Study design
6 conditions, mostly in triplicate
TFE3 rescue, FLAG, ×15 TFE3 rescue, H3K27Ac, ×15 TFE3-KO, FLAG, ×3 UOK109 cells, TFE3 rescue, FLAG, ×3 TFE3-KO, H3K27Ac, ×3 UOK109 cells, TFE3 rescue, H3K27Ac, ×3 TFE3-KO, Rabbit IgG CUT&RUN Negative Control … ×1

Supports a between-group comparison across 42 samples.

How we read this: 6 replicated groups read from 43 sample titles; they account for 42 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

+ 3 more — browse all 43 samples with per-sample file links →

Datasets on a similar topic

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