Adenot P G, Mercier Y, Renard J P, Thompson E M
Unité de Biologie du Développement, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
Development. 1997 Nov;124(22):4615-25. doi: 10.1242/dev.124.22.4615.
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.
在小鼠胚胎中，转录激活始于第一个细胞周期的S/G2期，此时父本和母本染色质仍处于同一细胞质内各自独立的核实体中。此时，雄原核的转录活性高于雌原核。由于核小体八聚体中组蛋白的乙酰化对基因表达具有调控作用，我们研究了从精子进入到微量基因组激活及有丝分裂过程中，父本和母本染色质重塑期间组蛋白乙酰化的变化。我们发现：（1）成熟精子和中期II母本染色质均未检测到组蛋白H4高度乙酰化；（2）受精后即刻，高度乙酰化的H4与父本而非母本染色质相关，而在孤雌激活的卵母细胞中，母本染色质发生高度乙酰化；（3）在合子中，雄原核和雌原核之间高度乙酰化H4的水平和模式差异在G1期的大部分时间持续存在，此时组蛋白去乙酰化酶和乙酰转移酶已处于活跃状态；（4）当在S/G2期观察到转录差异时，雄原核和雌原核的H4高度乙酰化水平相当，且达到这种相当水平无需DNA复制；（5）与配子染色质上缺乏H4高度乙酰化相反，第一次有丝分裂时的染色体呈现出明显的H4高度乙酰化条带模式。这些结果表明，精子染色质最初在卵母细胞中高度乙酰化H4的储备方面比母本染色质更具竞争力，高度乙酰化的H4参与合子中组蛋白-鱼精蛋白交换过程，并且G1期雄原核和雌原核中H4乙酰化的差异通过DNA复制转化为S/G2期的转录差异。受精前，父本和母本染色质均未表现出H4高度乙酰化模式的记忆，但在第一个细胞周期结束时，即在2细胞期主要合子基因组激活之前，染色体已呈现出高度乙酰化的H4条带模式。
