During spermiogenesis, haploid spermatids undergo extensive chromatin remodeling 
events in which histones are successively replaced by more basic protamines to 
generate highly compacted chromatin. Here we show for the first time that H3K79 
methylation is a conserved feature preceding the histone-to-protamine transition 
in Drosophila melanogaster and rat. During Drosophila spermatogenesis, the 
Dot1-like methyltransferase Grappa (Gpp) is primarily expressed in canoe stage 
nuclei. The corresponding H3K79 methylation is a histone modification that 
precedes the histone-to-protamine transition and correlates with histone H4 
hyperacetylation. When acetylation was inhibited in cultured Drosophila testes, 
nuclei were smaller and chromatin was compact, Gpp was little synthesized, H3K79 
methylation was strongly reduced, and protamines were not synthesized. The Gpp 
isoform Gpp-D has a unique C-terminus, and Gpp is essential for full fertility. 
In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with 
active RNA polymerase II, which might point towards a conserved function in 
chromatin remodeling during the histone-to-protamine transition in both 
Drosophila and rat.