DIFFERENTIAL H4 ACETYLATION OF PATERNAL AND MATERNAL CHROMATIN PRECEDES DNA-REPLICATION AND DIFFERENTIAL TRANSCRIPTIONAL ACTIVITY IN PRONUCLEI OF 1-CELL MOUSE EMBRYOS

In the mouse embryo, transcriptional activation begins during S/G(2) p hase 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 th an the female pronucleus, Since acetylation of histones in the nucleos ome octamer exerts a regulatory influence on gene expression, we inves tigated changes in histone acetylation during the remodeling of patern al and maternal chromatin from sperm entry through to minor genome act ivation and mitosis, We found (1) neither mature sperm nor metaphase I I maternal chromatin stained for hyperacetylated histone H4; (2) immed iately following fertilization, hyperacetylated H4 was associated with paternal but not maternal chromatin while, in parthenogenetically act ivated oocytes, maternal chromatin became hyperacetylated; (3) in zygo tes, differential levels and patterns of hyperacetylated H4 between ma le and female pronuclei persisted throughout most of G(1) with histone deacetylases and acetyltransferases already active at this time; (4) when transcriptional differences are observed in S/G(2), male and fema le pronuclei have equivalent levels of H4 hyperacetylation and DNA rep lication was not required to attain this equivalence and (5) in contra st to the lack of H4 hyperacetylation on gametic chromatin, chromosome s at the first mitosis showed distinct banding patterns of H4 hyperace tylation, These results suggest that sperm chromatin initially out-com petes maternal chromatin for the pool of hyperacetylated H4 in the ooc yte, that hyperacetylated H4 participates in the process of histone-pr otamine exchange in the zygote, and that differences in H4 acetylation in male and female pronuclei during G(1) are translated across DNA re plication to transcriptional differences in S/G(2). Prior to fertiliza tion, neither paternal nor maternal chromatin show memory of H4 hypera cetylation patterns but, by the end of the first cell cycle, before ma jor zygotic genome activation at the 2-cell stage, chromosomes already show hyperacetylated H4 banding patterns.