In both mammalian and Drosophila spermatids, the completely histone-based 
chromatin structure is reorganized to a largely protamine-based structure. 
During this histone-to-protamine switch, transition proteins are expressed, for 
example TNP1 and TNP2 in mammals and Tpl94D in Drosophila. Recently, we 
demonstrated that in Drosophila spermatids, H3K79 methylation accompanies 
histone H4 hyperacetylation during chromatin reorganization. Preceding the 
histone-to-protamine transition, the H3K79 methyltransferase Grappa is 
expressed, and the predominant isoform bears a C-terminal extension. Here, we 
show that isoforms of the Grappa-equivalent protein in humans, rats and mice, 
that is DOT1L, have a C-terminal extension. In mice, the transcript of this 
isoform was enriched in the post-meiotic stages of spermatogenesis. In human and 
mice spermatids, di- and tri-methylated H3K79 temporally overlapped with 
hyperacetylated H4 and thus accompanied chromatin reorganization. In rat 
spermatids, trimethylated H3K79 directly preceded transition protein loading on 
chromatin. We analysed the impact of bacterial infections on spermatid chromatin 
using a uropathogenic Escherichia coli-elicited epididymo-orchitis rat model and 
showed that these infections caused aberrant spermatid chromatin. Bacterial 
infections led to premature emergence of trimethylated H3K79 and hyperacetylated 
H4. Trimethylated H3K79 and hyperacetylated H4 simultaneously occurred with 
transition protein TNP1, which was never observed in spermatids of mock-infected 
rats. Upon bacterial infection, only histone-based spermatid chromatin showed 
abnormalities, whereas protamine-compacted chromatin seemed to be unaffected. 
Our results indicated that H3K79 methylation is a histone modification conserved 
in Drosophila, mouse, rat and human spermatids and may be a prerequisite for 
proper chromatin reorganization.