Zheng Ping, Patel Bela, McMenamin Malgorzata, Paprocki Ann Marie, Schramm R Dee, Nagl Norman G, Wilsker Deborah, Wang Xiaomei, Moran Elizabeth, Latham Keith E
The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Biol Reprod. 2004 May;70(5):1419-27. doi: 10.1095/biolreprod.103.023796. Epub 2004 Jan 14.
One of the most critical events of preimplantation development is the successful activation of gene transcription. Both the timing and the array of genes activated must be controlled. The ability to regulate gene transcription appears to be reduced just prior to the time of the major genome activation event, and changes in chromatin structure appear essential for establishing this ability. Major molecules that modulate chromatin structure are the linker and core histones, enzymes that modify histones, and a wide variety of other factors that associate with DNA and mediate either repressive or activating changes. Among the latter are chromatin accessibility complexes, SWI/SNF complexes, and the YY1 protein and its associated factors. Detailed information about the expression and regulation of these factors in preimplantation stage embryos has not been published for any species. In order to ascertain which of these factors may participate in chromatin remodeling, genome activation, and DNA replication during early primate embryogenesis, we determined the temporal expression patterns of mRNA encoding these factors. Our data identify the predominant members of these different functional classes of factors expressed in oocytes and embryos, and reveal patterns of expression distinct from those patterns seen in somatic cells. Among each of four classes of mRNAs examined, some mRNAs were expressed predominantly in the oocyte, with these largely giving way to others expressed stage specifically in the embryo. This transition may be part of a global mechanism underlying the transition from maternal to embryonic control of development, wherein the oocyte program is silenced and an embryonic pattern of gene expression becomes established. Possible roles for these mRNAs in chromatin remodeling, genome activation, DNA replication, cell lineage determination, and nuclear reprogramming are discussed.
着床前发育最关键的事件之一是基因转录的成功激活。基因激活的时间和激活的基因阵列都必须受到控制。在主要基因组激活事件发生之前,调节基因转录的能力似乎会降低,而染色质结构的变化对于建立这种能力似乎至关重要。调节染色质结构的主要分子是连接组蛋白和核心组蛋白、修饰组蛋白的酶,以及与DNA结合并介导抑制性或激活性变化的多种其他因子。后者包括染色质可及性复合物、SWI/SNF复合物以及YY1蛋白及其相关因子。关于这些因子在任何物种着床前阶段胚胎中的表达和调控的详细信息尚未发表。为了确定这些因子中的哪些可能参与早期灵长类胚胎发育过程中的染色质重塑、基因组激活和DNA复制,我们确定了编码这些因子的mRNA的时间表达模式。我们的数据确定了在卵母细胞和胚胎中表达的这些不同功能类别的因子的主要成员,并揭示了与体细胞中所见模式不同的表达模式。在所检测的四类mRNA中,一些mRNA主要在卵母细胞中表达,这些mRNA在很大程度上被胚胎中阶段特异性表达的其他mRNA所取代。这种转变可能是发育从母体控制向胚胎控制转变的整体机制的一部分,其中卵母细胞程序被沉默,基因表达的胚胎模式得以确立。本文讨论了这些mRNA在染色质重塑、基因组激活、DNA复制、细胞谱系确定和核重编程中的可能作用。