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A Repressive Type of TEAD4 Condensation and Engineering a Glue Peptide Therapy Against Cancer [RNA-Seq_TEAD4KO]

GSE255046 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/04/19 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples: 3 × NCctrl vs 3 × NCH vs 3 × T4ctrl vs 3 × T4HGroups 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.
Summary (written by the submitters)
Transcriptional factors (TFs) act as central determinants to coordinate cell death and survival by differentially modulating gene expression. Here, we systematically identified many TFs including TEAD4 forming condensates in stressed cells. In sharp contrast to YAP-induced transcription-activating condensation of TEAD4, we found co-factors such as VGLL4 and RFXANK could alternatively induce repressive condensation of TEAD4 to trigger cell death.
Read the full summary ↓
Illustrated by VGLL4, we mechanistically revealed that the heterotypic interactions between TEAD4 with VGLL4 favors its oligomerization and assembly of large condensates to manifest a nonclassical inhibitory function of this transcription factor, i.e., causing DNA/chromatin to be aggregated and entangled, which eventually impede gene expression. Based on these findings, we engineered a linker peptide (GLUP) to selectively “glue” TEAD4 molecules together, therefore forcefully driving its repressive condensation against YAP-induced activation. This glue peptide displayed a strong antitumor effect via inhibition of TEAD4-related gene transcription. Collectively, this work revealed a new type of phase separation, i.e., repressive condensation of TFs, and revealed how cofactor-induced differential condensation orchestrate opposite functions of a given TF, and further developed a new class of antitumor strategy by artificially inducing repressive condensation.
This dataset
Open GSE255046 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 GSE255046_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 PRJNA1073416 and SRA study SRP488128. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × NCctrl vs 3 × NCH vs 3 × T4ctrl vs 3 × T4H

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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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.