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Direct Inhibition of Tumor Hypoxia Response with Synthetic Transcriptional Repressors

GSE198157 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 31 samples Submitted 2024/06/22 Platform GPL24676Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 31 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
Mus musculus (mouse)
Samples
31 samples: 5 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
Direct inhibition of tumor hypoxia response with synthetic transcriptional repressorsNature chemical biology · 2025
Summary (written by the submitters)
Many oncogenic transcription factors (TFs) are considered to be undruggable due to their reliance on large protein-protein and protein-DNA interfaces. TFs like hypoxia-inducible factors (HIFs) and X-box binding protein 1 (XBP1) are induced by hypoxia and other stressors in solid tumors and bind to UPRE/HRE motifs to control oncogenic gene programs.
Read the full summary ↓
Here, we report a strategy to create synthetic transcriptional repressors (STRs) that mimic the bZIP domain of XBP1 and recognize the UPRE/HRE motif. A lead molecule, STR22, binds UPRE/HRE DNA sequences with high fidelity and competes with both TFs in cells. Under hypoxia, STR22 globally suppresses HIF1a binding to HRE-containing promoters/enhancers, inhibits hypoxia-induced gene expression and blocks pro-tumorigenic phenotypes in TNBC cells. In vivo, intratumoral and systemic STR22 treatment inhibited hypoxia-dependent gene expression, primary tumor growth and metastasis of TNBC tumors. These data validate a novel strategy to target the tumor hypoxia response through coordinated inhibition of TF-DNA binding.
Published in
Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors
Qiao Z, Nguyen LC, Yang D et al. · Nature chemical biology 2025 · PMID 39215099 · doi:10.1038/s41589-024-01716-z
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 GSE198157_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 PRJNA813878 and SRA study SRP363057. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly in triplicate
Mouse tumor PBS treatment # ×5 Mouse tumor STR22 treatment # ×5 Normoxia ×3 Hypoxia ×3 Hypoxia with STR22 ×3 Replicate 1 normoxia input ×1 Replicate 1 hypoxia input ×1 Replicate 1 hypoxia with STR22 input ×1 +9 more

Supports a between-group comparison across 19 samples.

How we read this: 5 replicated groups read from 31 sample titles; they account for 19 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
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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.