Abstract
ABSTRACTIn 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 μm to 700 μm in diameter, and these NDs are precisely localized in the post acrosome region (PAR), outside the sperm's core chromatin. Further, NDs exist mainly in sperm from fertile men in a pilot survey with a small sample size. Together, this study uncovers a new spatially-restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm, which might represent a novel mark for healthy sperm in human.
Highlights
In animal sperm, genomic DNA is mainly packaged by sperm nuclear basic proteins (SNBPs), which include protamines, protamine-like proteins and H1 histone-type proteins (Bloch and Teng, 1969; Ausió et al, 1999)
Though where nucleosomes are localized in the mammalian sperm genome remains controversial, it is a generally consistent view that retained nucleosomes in the sperm influence embryonic development and epigenetic inheritance (Gatewood et al, 1987; Hammoud et al, 2009; Carone et al, 2014; Samans et al, 2014)
It is hypothesized that sequence-specific nucleosome positioning (NP) facilitates sperm chromatin decondensation (SCD) upon fertilization, and that the position represents the start site of SCD (Gatewood et al, 1987)
Summary
Genomic DNA is mainly packaged by sperm nuclear basic proteins (SNBPs), which include protamines, protamine-like proteins and H1 histone-type proteins (Bloch and Teng, 1969; Ausió et al, 1999). Most of the retained nucleosomes are enriched in certain loci of the genome, such as imprinted genes and HOX genes, which are crucial for embryo development and can serve as epigenetic mark (Hammoud et al, 2009). This nucleosomeassociated epigenetic information, such as histone H3 lys demethylation, in human and mouse sperm has been shown to be involved in spermatogenesis and cellular homeostasis, and has been used to mark developmental regulators by histone H3 Lys trimethylation (Brykczynska et al, 2010)
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