Knocking down flr-4 transcriptionally activates the XDP genes in a p38 MAPK-dependent manner.

(A) Enrichment of genes involved in xenobiotic metabolism among those that are upregulated when flr-4 is knocked down using RNAi in WT, in comparison to control RNAi. Gene expression profiling was performed using RNA-seq and GO analysis performed using DAVID. Day 1 adult worms were used for RNA-seq. (B) Quantitative RT-PCR validation of expression of selected xenobiotic detoxification pathway (XDP) genes that were found to be upregulated using RNA-seq. (C) The expression of XDP genes is upregulated in WT in a sek-1-depdendent manner when flr-4 is knocked down. (D) In the nhr-8(ok168) mutant, life span is not extended when flr-4 is knocked down. (E) Knocking down vhp-1 using RNAi induced expression of GFP in cyp-35B1p::gfp but not in the nhr-8(ok186);cyp-35B1p::gfp transgenic worms. Images are of worms 48 hours post L4. Tails are marked by ‘T’. Images captured at 100x magnification. (F) The expression of ugt-18, cyp-33A1 and cyp-33C8 are not upregulated in nhr-8(ok186) to the same extent as in WT, when vhp-1 is knocked down using RNAi. Day 1 adult worms were used for RNA-seq and QRT-PCR. Error bar indicates SEM. ****P≤0.0001, ***P≤0.001, **P≤0.01, *P≤0.05, n.s. not significant, Student’s t test.