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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 |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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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 reduced representation bisulfite sequencing (RRBS) to depict DNA methylation in control and SPOP F133V stably expressed 22Rv1 cells. Genomic DNA of cells are extracted and treated with restriction enzyme and followed by bisulfite sequencing to enrich for areas of the genome with a high CpG content. 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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| Overall design |
Examination of DNA methylation in SPOP WT and SPOP F133V Pca cell line.
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| Contributor(s) |
Huang H, Zhang J, Wang L, Ye Z, Wei T |
| Citation(s) |
34588438 |
| |
| Submission date |
Jul 31, 2020 |
| Last update date |
Oct 31, 2021 |
| Contact name |
Ting Wei |
| Organization name |
Mayo Clinic
|
| Street address |
507 3rd St SW
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55902 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA649940 |
| SRA |
SRP274577 |
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