A maternal store of macroH2A is removed from pronuclei prior to onset of somatic macroH2A expression in preimplantation embryos
A maternal store of macroH2A is removed from pronuclei prior to onset of somatic macroH2A expression in preimplantation embryos
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DOI：
10.1016/j.ydbio.2004.11.032
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发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Rasmussen, TP
中科院分区：
文献类型：
--
作者：
Chang, CC;Ma, YH;Rasmussen, TP
MacroH2A历史是典型的历史H2A的变体，在脊椎动物中是保守的。以前的研究已经表明，大分子过氧化氢与表观遗传基因沉默事件有关，包括X染色体失活。在这里，我们证明了在发育和成熟的小鼠卵母细胞中存在宏H_2A。在发育后期(Ig-GV)和发育完全(FG-GV)的卵母细胞中，MacroH_2A均定位于生发泡(GV)染色质。此外，在成熟卵母细胞的染色体上还含有大量的大分子H_2A，第一极体中含有丰富的大分子H_2A。然而，在正常受精产生的受精卵中，母体的大H_2A在后期2原核(2PN)阶段就会丢失。除残留极体外，2-、4-和8-细胞期的正常胚胎缺乏大分子H_2A。MacroH_2A蛋白在8-细胞期后在胚胎中重新表达，并持续存在于桑椹胚和囊胚中，其中核的MacroH_2A在滋养外胚层和内细胞团细胞中都存在。我们跟踪观察了卵母细胞激活产生的孤雌胚胎中原核中大分子H_2A的丢失。大量的大分子H_2A存在于中期II平板上，并持续到孤雌生殖后期，但在同核受精之前的原核解缩过程中逐渐丢失。对卵胞浆内单精子注射(ICSI)产生的胚胎的检查表明，在晚期原核阶段胚胎丢失之前，宏H_2A仅与雌性原核有关。这些结果概述了一个令人惊讶的发现，即在同核配子之前，母体储存的宏H_2A被从母体基因组中移除，导致胚胎在胚胎开始表达宏H_2A之前，在没有宏H_2A的情况下执行三到四个有丝分裂。(C)2004 Elsevier Inc.保留所有权利。
MacroH2A histories are variants of canonical historic H2A that are conserved among vertebrates. Previous studies have implicated macroH2As in epigenetic gene-silencing events including X chromosome inactivation. Here we show that macroH2A is present in developing and mature mouse oocytes. MacroH2A is localized to chromatin of germinal vesicles (GV) in both late growth stage (Ig-GV) and fully grown (fg-GV) stage oocytes. In addition, macroH2A is associated with the chromosomes of mature oocytes, and abundant macroH2A is present in the first polar body. However, maternal macroH2A is lost from zygotes generated by normal fertilization by the late 2 pronuclei (2PN) stage. Normal embryos at 2-, 4-, and 8-cell stages lack macroH2A except in residual polar bodies. MacroH2A protein expression reappears in embryos after the 8-cell stage and persists in morulae and blastocysts, where nuclear macroH2A is present in both the trophectodermal and inner cell mass cells. We followed the loss of macroH2A from pronuclei in parthenogenetic embryos generated by oocyte activation. Abundant macroH2A is present upon the metaphase II plate and persists through parthenogenetic anaphase, but macroH2A is progressively lost during pronuclear decondensation prior to synkaryogamy. Examination of embryos generated by intracytoplasmic sperm injection (ICSI) revealed that macroH2A is associated exclusively with female pronuclei prior to loss in late pronucleus stage embryos. These results outline a surprising finding that a maternal store of macroH2A is removed from the maternal genome prior to synkaryogamy, resulting in embryos that execute three to four mitotic divisions in the absence of macroH2A prior to the onset of embryonic macroH2A expression. (C) 2004 Elsevier Inc. All rights reserved.