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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 02, 2024 |
| Title |
Targeting transcriptional factor YY1 is synthetic lethal with loss of the histone demethylase KDM5C [CUT&Tag] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
In this study, we screened KDM5C-binding proteins and found that Yin Yang 1 (YY1) interacts with KDM5C. Interestingly, a synergistic antitumor effect was exerted when both KDM5C and YY1 were depleted, and targeting YY1 appeared to be a vulnerability in KDM5C-deficient cancer cells. Mechanistically, KDM5C is essential for global YY1 chromatin recruitment, especially at promoters. Moreover, an intact KDM5C JmjC domain but not KDM5C histone demethylase activity is required for KDM5C-mediated YY1 chromatin binding.Transcriptional profiling revealed that dual inhibition of KDM5C and YY1 led to significantly increased transcriptional repression of many cell cycle- and apoptosis-related genes. In summary, our work demonstrates a synthetic lethal interaction between YY1 and KDM5C and suggests a therapeutic vulnerability that can be targeted using combination therapies.
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| Overall design |
Cleavage Under Targets and Tagmentation (CUT&Tag) for KDM5C and YY1 in ACHN cells.
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| Contributor(s) |
Zheng Q, Xiong J, Li F |
| Citation(s) |
39433896 |
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| Submission date |
Aug 28, 2024 |
| Last update date |
Dec 03, 2024 |
| Contact name |
Jie Xiong |
| E-mail(s) |
jiexiong@whu.edu.cn
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| Organization name |
Wuhan University
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| Street address |
185, Donghu road
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| City |
Wuhan |
| ZIP/Postal code |
430071 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1153280 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE275838_RAW.tar |
199.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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