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Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth [Hi-C]

GSE193413 Homo sapiens (human) Other 28 samples Submitted 2024/05/08 Platform GPL20795Platform GPL20301
At a glance

human · 28 samples

Organism
Homo sapiens (human)
Samples
28 samples: 14 conditions, mostly in duplicateGroups 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.
Paper
Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growthNature structural & molecular biology · 2025
Summary (written by the submitters)
Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers need to be elucidated such as the working mode and whether they can form “super-silencers”. Here, through interrogating two putative silencer components of FGF18 gene, we found that two silencers can cooperate via compensated chromatin interactions to form the “super-silencer”.
Read the full summary ↓
Furthermore, double knock-out of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To disturb the “super-silencers”, we applied the combinational treatment of GSK343 and X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while any single treatment only had mild changes. Such changes of TADs and loops may due to the decreased CTCF proteins upon the GR treatment. Moreover, GSK343 and X5050 can work synergistically to upregulated the super-silencer controlled apoptotic genes, thus gave rise to antitumor effects including apoptosis, cell cycle arrest and tumor growth inhibition. Overall, our data demonstrated the first example of “super-silencer” and showed that combinational usage of GSK343 and X5050 maybe the potential drug to curing cancers through disruption of “super-silencers”.
Published in
Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth
Zhang Y, Chen K, Tang SC et al. · Nature structural & molecular biology 2025 · PMID 39304765 · doi:10.1038/s41594-024-01391-7
This dataset
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Download · which file do I need?

Direct links to NCBI, 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.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE193413_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

Also filed as BioProject PRJNA796228 and SRA study SRP354438. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39304765) ↗
Study design
14 conditions, mostly in duplicate
DMSO ×2 GSK343 ×2 X5050 ×2 combined 72H ×2 combined 8H ×2 combined 24H ×2 EV ×2 S1KO ×2 +6 more

Supports a between-group comparison across 28 samples.

How we read this: 14 replicated groups read from 28 sample titles; they account for 28 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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