AUTHOR=Herz Hans-Martin , Bergmann Andreas 

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

JOURNAL=Frontiers in Cell Death

VOLUME=3

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-death/articles/10.3389/fceld.2024.1471050

DOI=10.3389/fceld.2024.1471050

ISSN=2813-5563

ABSTRACT=<p>We conducted an EMS mutagenesis screen on chromosome arm 2L to identify recessive suppressors of <italic>GMR-hid</italic>-induced apoptosis in the <italic>Drosophila</italic> eye. Through this screen, we recovered three alleles of the lysine demethylase gene <italic>Kdm5</italic>. 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 <italic>Kdm5</italic>. Interestingly, <italic>GMR-hid</italic>-induced apoptosis is suppressed independently of Kdm5’s demethylase activity. Our findings indicate that Rbf and dMyc are necessary for <italic>Kdm5</italic> mosaics to suppress <italic>GMR-hid</italic>-induced cell death. Moreover, <italic>Kdm5</italic> mosaics failed to suppress apoptosis induced by a mutant form of Hid that is resistant to inhibition by Erk-type MAPK activity. Additionally, <italic>Kdm5</italic> 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.</p>