Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.

• MeSH
• acetylace MeSH
• chromatin * metabolismus   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• myši MeSH
• nukleozomy * metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• protaminy metabolismus   MeSH
• restrukturace chromatinu MeSH
• sperma metabolismus   MeSH
• spermatidy metabolismus   MeSH
• spermatogeneze fyziologie   MeSH
• spermie metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The hypodactylous (hd) locus impairs limb development and spermatogenesis, leading to male infertility in rats. We show that the hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene. The retroviral insertion in hd mutant rats disrupts the normal splicing of Cntrob transcripts and results in the expression of a truncated protein. During the final phase of spermiogenesis, centrobin localizes to the manchette, centrosome, and the marginal ring of the spermatid acroplaxome, where it interacts with keratin 5-containing intermediate filaments. Mutant spermatids show a defective acroplaxome marginal ring and separation of the centrosome from its normal attachment site of the nucleus. This separation correlates with a disruption of head-tail coupling apparatus, leading to spermatid decapitation during the final step of spermiogenesis and the absence of sperm in the epididymis. Cntrob may represent a novel candidate gene for presently unexplained hereditary forms of teratozoospermia and the "easily decapitated sperm syndrome" in humans.

• MeSH
• bičík spermie metabolismus   MeSH
• blotting far-western MeSH
• centrozom metabolismus   MeSH
• elektronová mikroskopie MeSH
• endogenní retroviry genetika   MeSH
• epididymis metabolismus   MeSH
• fluorescenční protilátková technika MeSH
• hlavička spermie metabolismus   MeSH
• homeoboxové geny genetika   MeSH
• homeodoménové proteiny metabolismus   MeSH
• introny genetika   MeSH
• keratin-5 genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• mutace genetika   MeSH
• mužská infertilita genetika   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny buněčného cyklu fyziologie   MeSH
• spermatidy metabolismus   MeSH
• spermatogeneze genetika   MeSH
• transport proteinů genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH