Increased Glycine-N-methyltransferase expression disrupts light-dependent gene expression rhythms in the Drosophila...

Glycine-N-methyltransferase (Gnmt) is highly upregulated in the aging Drosophila melanogaster eye. Gnmt regulates S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) availability by catalyzing the transfer of a methyl group from SAM to glycine, producing sarcosine and SAH. Gnmt is well studied in the liver; however, little is known about the consequences of increased Gnmt in neurons. We overexpressed Gnmt in the eye and profiled diurnal rhythmic gene expression and histone methylation in photoreceptor neurons. Here, we show that eye-specific Gnmt overexpression altered rhythmic gene expression without impacting photoreceptor viability. Gnmt overexpression decreased global repressive histone methylation but had no major effect on H3K4 methylation, suggesting that methylation reactions are selectively inhibited by Gnmt and that Gnmt disrupts rhythmic gene expression independently of H3K4 methylation. Gnmt overexpression did not alter rhythmicity of core clock genes and did not impact circadian behavior. These results suggest that Gnmt plays a role in the regulation of light-dependent rhythmic gene expression in photoreceptors that does not involve the molecular clock.