O-GlcNAcome and Phosphoproteome

ABSTRACT: Liver circadian clock and daily rhythmic transcriptome are highly responsive to metabolic cues generated from daily feeding activity. The mechanisms that mediate metabolic inputs to the whole rhythmic transcriptome are still under investigation. Here, we explored the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) that integrates circadian and metabolic signals, in the diurnal regulation of nuclear proteins. We found daily oscillation of overall nuclear protein O-GlcNAcylation in the liver of mice subjected to natural night time-restricted feeding (NRF). O-GlcNAcomic analysis revealed that 11.54% of 719 O-GlcNAcylated proteins are rhythmically O-GlcNAcylated. Proteins involved in gene expression were enriched, suggesting rhythmic O-GlcNAcylation may directly shape diurnal transcriptome. Furthermore, we showed that rhythmic O-GlcNAcylation could indirectly modulate diurnal transcriptome by interacting with phosphorylation. Specifically, several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. For example, O-GlcNAcylation may occur at a phosphor-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), regulating the stability and transcriptional output of CLOCK. Lastly, unnatural day time-restricted feeding (DRF) dampens O-GlcNAcylation rhythm, suggesting the disruption of diurnal transcriptome could be mediated by protein O-GlcNAcylation. In summary, our results provide mechanistic insights into metabolic regulation of diurnal transcriptome at PTM level and shed light on the deleterious effects of improper mealtimes.

INSTRUMENT(S): Dionex instrument model

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Joanna Chiu  

PROVIDER: MSV000094417 | MassIVE | Wed Mar 27 16:01:00 GMT 2024

REPOSITORIES: MassIVE