PLX244288

GSE121472: O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle [RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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 MYCs 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. SOURCE: Alfonso Urbanucci (alfonsourbanucci@gmail.com) - University of Oslo