Abstract
<title>Abstract</title> <p>Differential packaging of vertebrate sperm and egg genomes is evolutionarily conserved for hundreds of millions of years. Unlike oocytes, post-meiotic spermatid nuclei are thought to uniformly replace histones with transition proteins (TNPs) and, ultimately, with protamines, the small non-histone structural proteins. Tracking of endogenously tagged protamines overturns the classical model of paternal chromatin remodeling, revealing a direct histone-to-protamine-1 transition that occurs independently of both TNPs and protamine-2. Stage-resolved chromatin profiling across 26 spermatid datasets reveals that chromatin compaction is a programmed process that requires H4-hyperacetylation but is not instructed by it. Rather, chromatin remodeling is guided by the pre-meiotic 3D-architecture of the spermatid nucleus: i.e., compaction of the A-compartment precedes B-compartment. This compartment-encoded template for sperm nuclear remodeling suggests that male-specific protamine patterns can transmit pre-meiotic structural information to the zygote and may impact embryonic development.</p>