Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos

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Abstract
In the mouse embryo, transcriptional activation begins during S/G2 phase of the first cell cycle when paternal and maternal chromatin are still in separate nuclear entities within the same cytoplasm. At this time, the male pronucleus exhibits greater transcriptional activity than the female pronucleus. Since acetylation of histones in the nucleosome octamer exerts a regulatory influence on gene expression, we investigated changes in histone acetylation during the remodeling of paternal and maternal chromatin from sperm entry through to minor genome activation and mitosis. We found (1) neither mature sperm nor metaphase II maternal chromatin stained for hyperacetylated histone H4; (2) immediately following fertilization, hyperacetylated H4 was associated with paternal but not maternal chromatin while, in parthenogenetically activated oocytes, maternal chromatin became hyperacetylated; (3) in zygotes, differential levels and patterns of hyperacetylated H4 between male and female pronuclei persisted throughout most of G1 with histone deacetylases and acetyltransferases already active at this time; (4) when transcriptional differences are observed in S/G2, male and female pronuclei have equivalent levels of H4 hyperacetylation and DNA replication was not required to attain this equivalence and (5) in contrast to the lack of H4 hyperacetylation on gametic chromatin, chromosomes at the first mitosis showed distinct banding patterns of H4 hyperacetylation. These results suggest that sperm chromatin initially out-competes maternal chromatin for the pool of hyperacetylated H4 in the oocyte, that hyperacetylated H4 participates in the process of histone-protamine exchange in the zygote, and that differences in H4 acetylation in male and female pronuclei during G1 are translated across DNA replication to transcriptional differences in S/G2. Prior to fertilization, neither paternal nor maternal chromatin show memory of H4 hyperacetylation patterns but, by the end of the first cell cycle, before major zygotic genome activation at the 2-cell stage, chromosomes already show hyperacetylated H4 banding patterns.