Genomic analyses of H1 cells induced by FOXO1

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. Overall design: Examination of FOXO1 binding in H1 cells, including two replicates in H1.