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| Status |
Public on May 21, 2019 |
| Title |
O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. Here, we employed ChIP-seq to map chromatin-bound O-GlcNAc loci in prostate cancer cells and discovered that these overlap with sites of active transcription and MYC binding. Using RNA-seq, we show that inhibition of OGT promotes MYC-dependent transcriptional repression of mRNAs involved in G1-S transition. O-GlcNAc ChIP-seq regions are highly enriched to transcription start sites and identify the ‘GFY’-motif. Proteins binding to this motif have not been established and we use synthetic oligonucleotides as a bait to enrich protein complexes associated with this sequence. By comparing the unbiased proteomic data from oligonucleotide enrichment with proteomic data from O-GlcNAc and MYC ChIP-mass spectrometry, we identified host cell factor 1 (HCF-1) as an interaction partner of MYC. Inhibition of OGT disrupted the interaction between MYC and HCF-1, and compromised MYC’s ability to promote proliferation of prostate cancer cells in the absence of androgens. Reverse phase protein arrays identified a set of proteins involved in mitosis that are dependent on MYC and OGT activity for expression. In conclusion, we show that OGT activity regulates MYC-driven proliferation by coordinating transcription and translation of cell cycle genes.
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| Overall design |
two biological replicates for prostate cancer cell line (LNCaP) overexpressing MYC gene under the control of Doxycycline. Differential expressed genes were retreaved for these cells treated for 4 and 24 hours with Doxycycline, OSMI2 (a OGT inhibitor), or a cmbination of both (combo) versus the vehicle treated cells (DMSO)
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| Contributor(s) |
Itkonen HM, Urbanucci A, Martin SE, Khan A, Mathelier A, Thiede B, Walker S, Mills IG |
| Citation(s) |
31149037 |
| |
| Submission date |
Oct 18, 2018 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Alfonso Urbanucci |
| E-mail(s) |
[email protected]
|
| Phone |
45048687
|
| Organization name |
Oslo University Hospital
|
| Street address |
Trondheimsveien 8
|
| City |
Oslo |
| State/province |
Oslo |
| ZIP/Postal code |
0560 |
| Country |
Norway |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE121474 |
O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle |
|
| Relations |
| BioProject |
PRJNA497432 |
| SRA |
SRP166092 |
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