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| Status |
Public on Dec 20, 2020 |
| Title |
An epigenetic mechanism underlying chromosome 17p deletion-driven tumorigenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromosome copy number variations are a hallmark of human cancers and among them chromosome 17p loss is the most common one and associated with poor prognosis. Our previous work demonstrates that 17p deletions can promote tumorigenesis more than p53 loss. Herein, with multiple functional genetic strategies, we identify a new 17p tumor suppressor, PHD finger protein 23 (PHF23). PHF23 deficiency impaires B cell differentiation and promotes Myc-driven lymphoma. Mechanistically, PHF23, a H3K4me3 reader, directly binds and represses the deacetylation activity of the SIN3-HDAC complex through its N-terminus, which coordinates two major active histone markers H3K4me3 and H3K27ac for activation of downstream B cell-differentiation genes and tumor suppressors. Further, we show that dysregulation of the PHF23-SIN3-HDAC complex is essential for PHF23 deficiency-induced tumorigenesis and maintenance. Hence, our study reveals a novel epigenetic regulatory mechanism that contributed to the pathology of 17p deleted cancers and suggests novel susceptibility of this miserable disease.
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| |
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| Overall design |
Bulk RNAseq on shPhf23 and shRen(control) in both pre-B cells and lymphoma cells.
Bulk RNAseq on Hdac_inhibitor-treated lymphoma cells. CHIP-seq on PHF23, HDAC1, H3K4me3 and H3K27ac in Ba/F3 cells. Drug 264 is Chidamide (Tucidinostat); drug 67 is Entinostat.
|
| Web link |
https://cancerdiscovery.aacrjournals.org/content/early/2020/12/18/2159-8290.CD-20-0336
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| |
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| Contributor(s) |
Chen M, Chen X, Pan X, Chen C, Liu Y |
| Citation(s) |
32978226 |
| |
| Submission date |
Feb 12, 2020 |
| Last update date |
Dec 22, 2020 |
| Contact name |
Xaingyu Pan |
| E-mail(s) |
[email protected]
|
| Organization name |
Sichuan University
|
| Department |
State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.
|
| Lab |
Chen & Liu Lab
|
| Street address |
No.17 Renming road section3
|
| City |
Chengdu, Cihna |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
| |
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| Platforms (2) |
| GPL23479 |
BGISEQ-500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (35)
|
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| Relations |
| BioProject |
PRJNA606276 |
| SRA |
SRP248452 |
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