The histone demethylase Kdm5 controls Hid-induced cell death in Drosophila

We conducted an EMS mutagenesis screen on chromosome arm 2L to identify recessive suppressors of <i>GMR-hid</i>-induced apoptosis in the <i>Drosophila</i> eye. Through this screen, we recovered three alleles of the lysine demethylase gene <i>Kdm5</i>. Kdm5, a member of the JmjC-domain-containing protein family, possesses histone demethylase activity towards H3K4me3. Our data suggest that Kdm5 specifically regulates Hid-induced cell death during development, as we did not observe control of Reaper- or Grim-induced cell death by <i>Kdm5</i>. Interestingly, <i>GMR-hid</i>-induced apoptosis is suppressed independently of Kdm5's demethylase activity. Our findings indicate that Rbf and dMyc are necessary for <i>Kdm5</i> mosaics to suppress <i>GMR-hid</i>-induced cell death. Moreover, <i>Kdm5</i> mosaics failed to suppress apoptosis induced by a mutant form of Hid that is resistant to inhibition by Erk-type MAPK activity. Additionally, <i>Kdm5</i> dominantly enhances the wing phenotype of an activated MAPK mutant. These results collectively suggest that Kdm5 controls Hid-induced apoptosis by regulating the Rbf, dMyc, and MAPK pathways.