Figure 1. UNC-62 binds age-regulated genes and modulates lifespan.

(A) Adult-specific knockdown of unc-62 extends lifespan by 30%. Approximately 150 day 1 adult wild-type (N2) worms were placed on bacteria expressing dsRNA targeting either unc-62, or control bacterial containing an empty vector. The x-axis indicates days of adulthood, and the y-axis indicates the percent of worms that remain alive at that age. The lifespan assay was performed five times (p<10⁻⁵ for each assay; one representative lifespan assay is shown). See Table S2 for lifespan data. (B) Hox co-factor UNC-62 Homothorax/Meis targets in day 4 of adulthood (Young Adults) show significant overlap with age-regulated transcripts [10], [18]. Only factor-specific binding sites bound by less than 10 out of 57 transcription factors profiled by the modENCODE consortium were utilized. Enrichment p-value was determined by Fisher's Exact test. (C) Schematic of the UNC-62:GFP fosmid used to generate an UNC-62 fluorescent reporter. A GFP tag was inserted at the C-terminus of UNC-62 in a fosmid containing all unc-62 exons and introns, as well as ∼18.5 kb of 5′ promoter sequence. (D) The UNC-62:GFP fosmid-based transgene can rescue the embryonic lethality defects of both an unc-62 null mutation (s472; denoted −) as well as a weaker mutation in unc-62 exon 7b (e644, denoted 7b(−)) [13]. 7b(+) refers to a transgene that expresses only the unc-62 exon 7b isoform. Circles indicate the number of viable progeny observed from 5 unmated hermaphrodites of each genotype, with the mean indicated by a horizontal line. (E) In hermaphrodites, UNC-62:GFP is expressed in intestine (int), neurons (neu), ventral nerve cord (vnc), vulval precursor cells (not shown), and (right) hypodermis (hyp). UNC-62 intestinal expression is stage-specific: intestine expression in L2 and earlier stages is weak or not visible (top), whereas intestinal expression is dramatically induced by the L4 stage (bottom).