O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle
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ABSTRACT:
PROVIDER: PRJNA497434 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle [ChIP-seq]
| PRJNA448681 | ENA
Project description:O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle [RNA-seq]
| PRJNA497432 | ENA
Project description: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.
2019-05-21 | GSE112667 | GEO
Project description: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.
2019-05-21 | GSE121472 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-21 | GSE121474 | GEO
Project description:Single cell RNA sequencing, 5 week deletion of O-GlcNAc transferase (OGT) in hepatocytes
2023-11-08 | GSE223830 | GEO
Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. In C. elegans, three mutant strains(genotypes used: N2 (wild-type), ogt-1 (ok1474), oga-1 (ok1207), and pmk-1 (km25)) were treated with the human pathogen S. aureus (SA) or P. aeruginosa(PA) and OP50 (E. coli control) with three biological replications.
2015-05-01 | E-GEOD-53732 | biostudies-arrayexpress
Project description:O-GlcNAcylation is the modification of serine and threonine residues with beta-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. To investigate the role of protein O-GlcNAcylation on intestinal homeostasis, we generated intestinal epithelial cell (IEC)-specific O-GlcNAc transferase (OGT) knockout in mice. The KO mice developed spontanous intestinal inflammation. To determine the underlying molecular mechanisms, we performed RNA sequencing of ileum and colon epithelial cells of wildtype and IEC-OGT KO mice.
2017-06-27 | GSE100473 | GEO
Project description:An X-chromosome exome sequencing analysis identified a mutation in O-GlcNAc transferase (OGT) (pL254F) in a family with X-linked intellectual disability (XLID). Affected patient lymohoblastoids exhibit decreased steady state OGT levels owing to an unstable protein compared to the unaffected, related male controls. Suprisingly, global O-GlcNAc levels remained remained unaltered. This prompted us to check the both protein and mRNA levels of the other cycling enzyme, O-GlcNAcase (OGA) which was also lowered. This implies that a compensation mechanism exists, however imperfect, owing to the disease state of the individuals. We performed glabal transcriptome analysis to assess any other changes in message between patients and controls. Our study highlights small differences in the global transcriptome of patient lymhoblastoids that have the L254F mutation in O-GlcNAc transferase when compared to familial controls using Illumina sequencing of total RNA
2016-02-25 | E-GEOD-74263 | biostudies-arrayexpress
Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.
2015-05-01 | GSE53732 | GEO