Human sperm chromatin forms spatially restricted nucleosome domains consistent with programmed nucleosome positioning

In human sperm, a fraction of its chromatin retains nucleosomes that are positioned on specific sequences containing genes and regulatory units essential for embryonic development. This nucleosome positioning (NP) feature provides an inherited epigenetic mark for sperm. However, it is not known whether there is a structural constraint for these nucleosomes and, if so, how they are localized in a three-dimensional (3D) context of the sperm nucleus. In this study, we examine the 3D organization of sperm chromatin and specifically determine its 3D localization of nucleosomes using structured illumination microscopy. A fraction of the sperm chromatin form nucleosome domains (NDs), visible as microscopic puncta ranging from 40 m to 700 m in diameter, and these NDs are precisely localized in the postacrosome region (PAR), outside the sperms core chromatin. Importantly, these types of NDs exist only in sperm from fertile men but not in sperm from sterile men. This study uncovers a new spatially restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm. This represents a novel form of epigenetic mark for healthy sperms and can provide a potential new therapeutic and diagnostic target for treating male infertility.