Department of Genetics, Justus Liebig University Giessen, Heinrich-Buff-Ring 58-62, 35392 Giessen, Germany
Sudhanshu Bhushan
Unit of Reproductive Biology, Department of Anatomy and Cell Biology, Justus Liebig University Giessen, Aulweg 123, 35385 Giessen, Germany
Klaus Steger
Molecular Andrology Section, Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany
Andreas Meinhardt
Unit of Reproductive Biology, Department of Anatomy and Cell Biology, Justus Liebig University Giessen, Aulweg 123, 35385 Giessen, Germany
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.
