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| Status |
Public on Apr 19, 2024 |
| Title |
A Repressive Type of TEAD4 Condensation and Engineering a Glue Peptide Therapy Against Cancer [ChIP-Seq 1] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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. 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.
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| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K27ac，H3K27me3 in GLUP peptide treated HGC-27 cells.
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| Contributor(s) |
Tang Y, An L, Zhang H |
| Citation missing |
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| Submission date |
Sep 30, 2023 |
| Last update date |
Apr 20, 2024 |
| Contact name |
yang tang |
| E-mail(s) |
tangyang2013@sibcb.ac.cn
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| Organization name |
Shanghai Institute of Biochemistry and Cell Biology
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| Street address |
Yueyang Road 320
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| City |
shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE244420 |
A Repressive Type of TEAD4 Condensation and Engineering a Glue Peptide Therapy Against Cancer |
|
| Relations |
| BioProject |
PRJNA1022822 |
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