GEO series
Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth [Hi-C]
Summary
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”. 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
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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Direct links to NCBI, no account and no request form: the whole study as GSE193413_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples.
Also filed as BioProject PRJNA796228 and SRA study SRP354438. Searching any of these in the dataset finder brings you back here.
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.
14 replicated groups read from 28 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM5799884 DMSO rep1
- GSM5799885 DMSO rep2
- GSM5799886 GSK343 rep1
- GSM5799887 GSK343 rep2
- GSM5799888 X5050 rep1
- GSM5799889 X5050 rep2
- GSM5799890 combined 72H rep1
- GSM5799891 combined 72H rep2
- GSM5799892 combined 8H rep1
- GSM5799893 combined 8H rep2
- GSM5799894 combined 24H rep1
- GSM5799895 combined 24H rep2
- GSM5799896 EV rep1
- GSM5799897 EV rep2
- GSM5799898 S1KO rep1
- GSM5799899 S1KO rep2
- GSM5799900 S2KO rep1
- GSM5799901 S2KO rep2
- GSM5799902 DKO rep1
- GSM5799903 DKO rep2
- GSM7663154 siCTCF rep1
- GSM7663155 siCTCF rep2
- GSM7663156 siscramble rep1
- GSM7663157 siscramble rep2
- GSM7663158 ETS rep1
- GSM7663159 ETS rep2
- GSM7663160 control rep1
- GSM7663161 control rep2
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