|
| Status |
Public on Dec 12, 2022 |
| Title |
PALI1 Promotes Tumor Growth through Competitive Recruitment of PRC2 to G9A-target Chromatin for Dual Epigenetic Silencing |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
PALI1 is a newly identified accessory protein of the Polycomb Repressive Complex 2 (PRC2) that catalyzes H3K27 methylation. However, the roles of PALI1 in cancer are yet to be defined. Here we report that PALI1 is upregulated in advanced prostate cancer (PCa) and competes with JARID2 for binding to PRC2 core subunit SUZ12. PALI1 further interacts with the H3K9 methyltransferase G9A, bridging the formation of a unique G9A-PALI1-PRC2 super-complex that occupies a subset of G9A-target genes to mediate dual H3K9/K27 methylation and gene repression. Many of these genes are developmental regulators induced upon cell differentiation, and their loss in PCa predicts poor prognosis. Accordingly, PALI1 and G9A drive PCa cell proliferation and invasion in vitro and xenograft tumor growth in vivo. Collectively, our study shows that PALI1 harnesses two central epigenetic mechanisms to suppress cellular differentiation and promote tumorigenesis, which can be targeted by dual EZH2 and G9A inhibition.
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| |
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| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
36476474 |
| Submission date |
May 27, 2021 |
| Last update date |
Dec 14, 2022 |
| Contact name |
Jindan Yu |
| E-mail(s) |
jindan.yu@emory.edu
|
| Organization name |
Emory University
|
| Department |
Urology
|
| Lab |
Jindan Yu's lab
|
| Street address |
E330, 1760 Haygood Dr NE
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (54)
|
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| This SuperSeries is composed of the following SubSeries: |
| GSE175696 |
PALI1 Promotes Tumor Growth through Competitive Recruitment of PRC2 to G9A-target Chromatin for Dual Epigenetic Silencing [RNA-seq] |
| GSE182144 |
PALI1 Promotes Tumor Growth through Competitive Recruitment of PRC2 to G9A-target Chromatin for Dual Epigenetic Silencing [RNA-Seq II] |
| GSE212625 |
PALI1 Promotes Tumor Growth through Competitive Recruitment of PRC2 to G9A-target Chromatin for Dual Epigenetic Silencing [ChIP-seq] |
|
| Relations |
| BioProject |
PRJNA733210 |
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