{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE348nnn/GSE348433/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348433"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RBBP5 is an epigenetic regulator of mammalian hepatic 12h oscillator","description":"Proteostasis is essential for cellular health, with its disruption contributing to aging, neurodegeneration, and metabolic disorders. While the upstream proteostatic stress-sensing and protein-folding mechanisms in the ER and cytosol are well studied, the transcriptional regulation of proteostasis remains incompletely understood, particularly concerning the temporal epigenome dynamics, chromatin landscapes, and co-regulatory networks underlying dynamic proteostasis control. Traditionally, proteostatic stress responses were viewed as acute reactions to noxious stimuli, but recent evidence shows that many proteostasis genes exhibit ~12-hour ultradian rhythms under physiological conditions, driven by a XBP1s-dependent oscillator independent of the canonical circadian clock and cell cycle. By mapping the chromatin landscape of the murine 12-hour oscillator, we identified RBBP5—an essential subunit of the COMPASS complex responsible for H3K4 trimethylation—as a pivotal epigenetic regulator of proteostasis dynamics. In contrast, histone acetyltransferases and H3K9 acetylation were dispensable for dynamic proteostasis gene expression. RBBP5 is not only indispensable for the 12-hour oscillator but also essential for the transcriptional regulation of diverse proteotoxic stresses response, by coactivating XBP1s and promoting H3K4me3 deposition at the promoters of proteostasis genes. As a result, loss of RBBP5 sensitizes cells to proteostatic stress due to impaired autophagy. Proximity labeling of H3K4me3 further uncovered a dynamic chromatin-associated proteomic architecture, including components of COMPASS, the Integrator complex and SWI/SNF remodelers, that constitutes the transcriptional response to proteostatic stress. Together, these findings establish RBBP5 as a central regulator of proteostasis dynamics, essential for maintaining cellular resilience.","dates":{"publication":"2026/09/23"},"accession":"GSE348433","cross_references":{"GSM":["GSM10072070","GSM10072081","GSM10072071","GSM10072080","GSM10072078","GSM10072079","GSM10072076","GSM10072077","GSM10072074","GSM10072075","GSM10072072","GSM10072073"],"GPL":["34290"],"GSE":["348433"],"taxon":["Mus musculus"]}}