Fig. 7.

Fifty-six hif-1–dependent genes show nonclassical antagonistic effects of vhl-1 and egl-9. (A) A total of 56 genes in C. elegans exhibit nonclassical epistasis in the hypoxia pathway, characterized by opposite effects on gene expression, relative to the wild type, of the vhl-1(lf) compared with egl-9(lf) [or rhy-1(lf)] mutants. Shown are a random selection of 15 out of 56 genes for illustrative purposes. (B) Genes that behave noncanonically have a consistent pattern. vhl-1(lf) mutants have an opposite effect to egl-9(lf), but egl-9 remains epistatic to vhl-1 and loss-of-function mutations in hif-1 suppress the egl-9(lf) phenotype. Asterisks show $\beta$ values significantly different from 0 relative to wild type ($q<{10}^{-1}$).