Abstract

Drosophila melanogaster is often considered to lack genomic 5‐methylcytosine (m5C), an opinion reinforced by two whole genome bisulfite‐sequencing studies that failed to find m5C. New evidence, however, indicates that genomic methylation is indeed present in the fly, albeit in small quantities and in unusual patterns. At embryonic stage 5, m5C occurs in short strand‐specific regions that cover ∼1% of the genome, at tissue levels suggesting a distribution restricted to a subset of nuclei. Its function is not obvious, but methylation in subsets of nuclei would obscure functional associations since transcript levels and epigenetic modifications are assayed in whole embryos. Surprisingly, Mt2, the fly's only candidate DNA methyltransferase, is not necessary for the observed methylation. Full evaluation of the functions of genome methylation in Drosophila must await discovery and experimental inactivation of the DNA methyltransferase, as well as a better understanding of the pattern and developmental regulation of genomic m5C.