Fig. 1: SET-26 and HCF-1 operate in the same genetic pathway to modulate lifespan and have overlapping binding profiles at chromatin.

a Survival curves for wildtype controls, set-26(-), hcf-1(-), and set-26(-) hcf-1(-) double mutants from one representative experiment (n = 101, 103, 105, and 106 worms, respectively). Source data are provided as a Source Data file. N = 2 biological replicates. Distribution of somatic (b) SET-26 or (c) HCF-1 peaks relative to the transcription start sites (TSS) of associated genes within 3 kb. Count represents the number of somatic peaks within each bin. Data were obtained from CUT&RUN assays (N = 2) in either glp-1(-);set-26::ha or glp-1(-);hcf-1::gfp::3xflag tagged strains. d Screenshot from the Integrated Genomics Viewer (IGV) showing a genome-wide view of somatic SET-26 or HCF-1 binding. Binding is displayed as normalized log2 signal, where blue represents enrichment, and red represents depletion, of factor binding relative to control. e This shows the same binding data as in (d) but for a portion of Chromosome IV. Binding is displayed on the top track, and peaks called by MACS2 are displayed on the bottom track, where the darker blue represents more statistically significant peaks as determined by MACS2. f Venn diagram showing somatic SET-26 and HCF-1 peaks in the glp-1(-) mutant background, and 7012 peaks showing an overlap of 1 bp or more. g Metaplots of normalized SET-26 and HCF-1 binding signals within the 7012 overlapping peak regions identified in (f). h Venn diagram showing the number of genes associated with somatic SET-26 or HCF-1 binding, and 8824 genes that are commonly bound by both factors. i Gene ontology (GO) term analysis for the 8824 genes bound by both SET-26 and HCF-1 in somatic cells as determined by Wormcat. In (f, h) *** indicates p < 1 × 10⁻¹⁵ and the overlap is higher than expected by chance, as calculated by one-sided hypergeometric test for peak overlap (in f) and one-sided Fisher’s Test for gene overlap (in h). In (i), Wormcat p values are determined by one-sided Fisher test with FDR correction. Peaks and gene sets are provided in Supplementary Data 2.