The histone demethylase Dmel\Kdm4A controls genes required for life span and male-specific sex determination in Drosophila.

Histone methylation plays an important role in regulating chromatin-mediated gene control and epigenetic-based memory systems that direct cell fate. Enzymes termed histone demethylases directly remove the methyl marks from histones, thus contributing to a dynamically regulated histone methylated genome; however, the biological functions of these newly identified enzymes remain unclear. The JMJD2A-D family belongs to the JmjC domain-containing family of histone demethylases (JHDMs). Here, we report the cloning and functional characterization of the Drosophila HDM gene Dmel\Kdm4A that is a homolog of the human JMJD2 family. We show that homologs for three human JHDM families, JHDM1, JHDM2, and JMJD2, are present in Drosophila and that each is expressed during the Drosophila lifecycle. Disruption of Dmel\Kdm4A results in a reduction of the male life span and a male-specific wing extension/twitching phenotype that occurs in response to other males and is reminiscent of an inter-male courtship phenotype involving the courtship song. Remarkably, certain genes associated with each of these phenotypes are significantly downregulated in response to Dmel\Kdm4A loss, most notably the longevity associated Hsp22 gene and the male sex-determination fruitless gene. Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in life span and male-specific sex determination in the fly.