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WSTF deficiency reprograms regulatory networks by linking locus‑specific chromatin remodeling to altered isoform expression and misdirected signaling [mRNA-seq]

GSE314625 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2025/12/24 Platform GPL24676Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 18 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
18 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
WSTF deficiency reprograms regulatory networks by linking locus-specific chromatin remodeling to altered isoform expression and misdirected signalingNucleic acids research · 2026
Summary (written by the submitters)
Loss of the chromatin remodeler WSTF (BAZ1B), a gene deleted in Williams syndrome, causes reproducible, genome-scale reprogramming of chromatin states and transcript processing that links altered chromatin composition to misprocessed transcripts and aberrant signaling.
Read the full summary ↓
Using engineered HCT116-WSTFKO cells and patient-derived Williams syndrome cell lines, we combine transcriptome profiling, microscopy, chromatin CUT&RUN, and histone post-translational modification (HPTM)-defined chromatin state modeling to show that WSTF localizes to promoters and gene bodies of actively transcribed loci together with ASH2L and CBP. Loss of WSTF causes depletion of ASH2L/CBP, selective loss of H3K4me2 and multiple acetylation marks, and gain of Polycomb components. This loss results in systematic conversion from a multi-mark active promoter/enhancer chromatin landscape to a hypoacetylated, H3K4me2-depleted, PRC-enriched landscape. These chromatin changes coincide with widespread isoform switching and splicing alterations in genes encoding chromatin regulators and signaling pathways. This WSTF deficiency produces Wnt/β-catenin hyperactivation. A locus-specific example at TCF7L2 demonstrates how gene body loss of active marks drives isoform switching that alters DNA binding domains and decouples stabilized nuclear β-catenin from canonical target engagement. Our results link signaling dysregulation to developmental pathway misregulation consistent with Williams syndrome phenotypes.
Published in
WSTF deficiency reprograms regulatory networks by linking locus-specific chromatin remodeling to altered isoform expression and misdirected signaling
Behrouz Sharif S, Dennis JH · Nucleic acids research 2026 · PMID 42258541 · doi:10.1093/nar/gkag602
This dataset
Open GSE314625 in finder → Find more human RNA-seq 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 GSE314625_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1392308 and SRA study SRP657202. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42258541) ↗
Study design
6 conditions, mostly in triplicate
Wild-type HCT116, technical ×3 HCT116_WSTFKO, bio-rep1, technical ×3 HCT116_WSTFKO, bio-rep2, technical ×3 GM14295, technical ×3 GM14296, technical ×3 GM14297, technical ×2 GM14297_technical ×1

Supports a between-group comparison across 17 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 17 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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