Genomic analyses of H1 cells induced by FOXO1
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ABSTRACT: Insufficient understanding on cold adaptation technically restricts donor tissue banking. Here we identify FOXO1 as a conserved transcription factor for cell cold survival, relocating from cytosol to nucleus when temperature drops. FOXO1 small ubiquitin-like modifiers (SUMO) -interacting motif (SIM) antagonizes FOXO1-Importin-7 interaction regardless of temperature. At 37°C, SIM enhances FOXO1 interactions with SUMO E3 ligase RANBP2 and Exportin-1, FOXO1 hence cytoplasmic; at 4°C, FOXO1-Importin-7 interaction increases probably via RANBP2, making FOXO1 nuclear. These features enable fine-tuned FOXO1 regulations on chromatin folding and subsequent gene expression. Using these key factors as readouts, a ‘hibernation solution’ was developed, enabling long-term pancreatic islet cold storage and transplantation to cure diabetes. Henceforth, targeting FOXO1 SIM or the SUMO machinery may aid tissue/organ survival from long-term cold and other stresses.
ORGANISM(S): Homo sapiens
PROVIDER: GSE183998 | GEO | 2024/03/01
REPOSITORIES: GEO
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