The DM domain transcription factor MAB-3 regulates male hypersensitivity to oxidative stress in Caenorhabditis elegans.

Sex differences occur in most species and involve a variety of biological characteristics. The nematode Caenorhabditis elegans consists of two sexes, self-fertile hermaphrodites (XX) and males (XO). Males differ from hermaphrodites in morphology, behavior, and life span. Here, we find that male C. elegans worms are much more sensitive than hermaphrodites to oxidative stress and show that the DM domain transcription factor MAB-3 plays a pivotal role in determining this male hypersensitivity. The hypersensitivity to oxidative stress does not depend on the dosage of X chromosomes but is determined by the somatic sex determination pathway. Our analyses show that the male hypersensitivity is controlled by MAB-3, one of the downstream effectors of the master terminal switch TRA-1 in the sex determination pathway. Moreover, we find that MAB-3 suppresses expression of several transcriptional target genes of the ELT-2 GATA factor, which is a global regulator of transcription in the C. elegans intestine, and show that RNA interference (RNAi) against elt-2 increases sensitivity to oxidative stress. These results strongly suggest that the DM domain protein MAB-3 regulates oxidative stress sensitivity by repressing transcription of ELT-2 target genes in the intestine.