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| Status |
Public on May 05, 2023 |
| Title |
VprBP/DCAF1 triggers melanomagenic gene silencing through histone H2A phosphorylation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
DCAF1, also known as VprBP, is a recently identified atypical kinase and plays an important role in downregulating the transcription of tumor suppressor genes as well as increasing the risk for colon and prostate cancers. Melanoma is the most aggressive form of skin cancer arising from pigment-producing melanocytes and is often associated with dysregulation of epigenetic factors targeting histones. Here we demonstrate that DCAF1 is highly expressed and phosphorylates threonine 120 (T120) on histone H2A to drive transcriptional inactivation of growth regulatory genes in melanoma cells. As is the case for its epigenetic function in other types of cancers, DCAF1 acts to induce gene silencing program dependently of H2AT120 phosphorylation (H2AT120p). The significance of DCAF1-mediated H2AT120p is further underscored by the fact that DCAF1 knockdown- or DCAF1 inhibitor-induced lockage of H2AT120p mitigates melanoma tumor growth in xenograft models. Collectively, our results establish DCAF1-mediated H2AT120p as a key epigenetic signal for melanomagenesis and suggest the therapeutic potential of targeting DCAF1 kinase activity for effective melanoma treatment.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for G361 cells (shCont, and shDCAF1).
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| Contributor(s) |
Shin Y, An W |
| Citation(s) |
37293029, 37760992 |
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| Submission date |
Apr 25, 2023 |
| Last update date |
Oct 04, 2023 |
| Contact name |
Yonghwan Shin |
| E-mail(s) |
[email protected]
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| Organization name |
University of Southern California
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| Department |
Biochemistry and Molecular Medicine
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| Lab |
NRT6517
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| Street address |
1450 Biggy St
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90033 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA961784 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230573_Processed_data-humanDCAF1-YS.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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