GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318171/primaryOK200TranscriptomicsCaenorhabditis elegansExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318171GEOGSEfalseNutrient-responsive and DAF-16/FoxO target H1 histone HIL-1 promotes resistance to starvation and bacterial pathogens in Caenorhabditis elegansInsulin/IGF-1 signaling (IIS) mediates metabolic and developmental acclimation to stressful conditions including starvation. The transcription factor DAF-16/FoxO actuates many of the physiological effects of reduced IIS, yet the specific contributions of DAF-16 target genes to stress resistance remain poorly understood. We explore the function of C. elegans H1 linker histone variant hil-1/H1.0, a DAF-16 target that is upregulated during starvation. The HIL-1 sequence is divergent from the other eight annotated C. elegans H1 variants, and the others are not so highly responsive to nutrient availability and DAF-16 activity, suggesting distinct function. Using knock-in reporters, we find that HIL-1 is expressed ubiquitously in nuclei of L1 and dauer larvae during starvation, but that expression is largely undetectable in fed larvae. Disrupting hil-1 activity through mutation or auxin-inducible degradation led to reduced growth after extended L1 starvation, revealing reduced starvation resistance. RNA-seq of hil-1 mutants showed that hil-1 affects expression of relatively few genes. However, hil-1 activates genes involved in the innate immune response, Pseudomonas aeruginosa infection, and components of the nipi-3/TRIB1 immunity pathway. hil-1 mutants display compromised survival upon exposure to P. aeruginosa under reduced IIS, and genes activated by hil-1 promote resistance to P. aeruginosa. Together these results suggest that DAF-16/FoxO activates transcription of hil-1 during starvation to promote resistance to starvation and pathogens. We demonstrate conditional regulation of an H1 histone, and we reveal a novel mechanism for how IIS promotes stress resistance by identifying a histone variant that connects nutrient sensing to immunity.2026/05/27GSE318171GSM9487919GSM9487918GSM9487917GSM9487916GSM9487927GSM9487926GSM9487925GSM9487924GSM9487923GSM9487922GSM9487921GSM948792034620318171Caenorhabditis elegans