The SET1/COMPASS subunit RBBP5 orchestrates epigenetic control of global proteostasis and the 12h oscillator to safeguard metabolic and cellular homeostasis.

ABSTRACT: Proteostasis is vital for cellular health, with disruptions leading to aging, neurodegeneration and metabolic disorders. Traditionally, proteotoxic stress responses were studied as acute reactions to various noxious factors; however, recent evidence reveals that many proteostasis genes exhibit ~12h ultradian rhythms under physiological conditions in mammals, driven by an XBP1s-dependent 12h oscillator. By examining the chromatin landscape of this oscillator, we identified RBBP5 as an essential epigenetic regulator of global proteostasis dynamics. Mechanistically, as the core subunit of the SET1/COMPASS complex, RBBP5 co-activates XBP1s to facilitate dynamic proteostasis gene expression by marking promoter-proximal H3K4me3, which further recruits the Integrator Complex and SWI/SNF chromatin

SUBMITTER: Kubra S 

PROVIDER: S-EPMC11419162 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature