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| Status |
Public on Aug 01, 2021 |
| Title |
SPOP mutations derived from prostate cancer establish a DNA hypermethylation epigenome through stabilizing GLP histone methyltransferase [methylation array] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Abnormal DNA methylation is one of the major factors driving oncogenesis and therapy resistance in cancer. The CULLIN3-RBX1 E3 ubiquitin ligase adaptor gene SPOP is the most frequently mutated gene in primary prostate cancers (PCa). SPOP-mutated prostate tumors strikingly associate with strongly elevated levels of genome-wide DNA hypermethylation, although the underlying mechanism remains elusive.We use Illumina Infinium MethylationEPIC BeadChip to depict DNA methylation in control and SPOP F102C stabily expressed 22Rv1 cells. Genomic DNA of cells are extracted and quantified by PicoGreen, followed by Illumina Infinium arrays. We find that SPOP mutant expression increases not only the overall cellular level of DNA methylation, but also specifically at loci of a subset of tumor suppressor genes (TSG) including FOXO3 and NDRG1, and this effect is mediated by GLP/G9a binding with DNMT proteins.These findings reveal a previously uncharacterized mechanism by which SPOP mutations promote DNA hypermethylation through stabilization GLP as a chromatin recruiter of DNMT. Our results also suggest that targeting DNA hypermethylation is a viable strategy for effective management of SPOP mutated PCa.
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| |
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| Overall design |
Examination of DNA methylation in SPOP WT and SPOP F102C Pca cell line
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| |
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| Contributor(s) |
Huang H, Zhang J, Wang L |
| Citation(s) |
34588438 |
| |
| Submission date |
Jun 30, 2021 |
| Last update date |
Oct 27, 2021 |
| Contact name |
LIGUO WANG |
| E-mail(s) |
[email protected]
|
| Organization name |
Mayo Clinic
|
| Department |
Division of Computational Biology
|
| Street address |
200 1st St SW
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL23976 |
Illumina Infinium HumanMethylation850 BeadChip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA742773 |
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