Majumder S, DePamphilis M L
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
J Cell Biochem. 1994 May;55(1):59-68. doi: 10.1002/jcb.240550107.
In mice, the first round of DNA replication occurs in fertilized eggs (1-cell embryos), while the onset of zygotic gene transcription begins approximately 20 hours after fertilization, a time that normally coincides with formation of a 2-cell embryo. One approach to investigating the mechanisms that control these developmentally regulated events has been to microinject plasmid DNA into the nuclei of mouse oocytes and embryos in order to determine the requirements for unique DNA sequences that regulate transcription and replication. The results from these and other studies have revealed two important mechanisms that regulate the beginning of animal development. The first is a time dependent "zygotic clock" of unknown detail that delays the onset of transcription, regardless of whether or not a 2-cell embryo is formed. The second is a mechanism that represses the activity of promoters and origins of replication specifically in maternal pronuclei of oocytes and 1-cell embryos, and in all nuclei of 2-cell embryos, regardless of their parental origin or ploidy. This repression is linked to chromatin, but the striking ability to relieve this repression with specific embryo-responsive enhancers first appears with formation of a 2-cell embryo. The need for a TATA-box to mediate enhancer stimulation of promoter activity appears even later when cell differentiation becomes evident. Thus, a biological clock delays transcription until both paternal and maternal genomes are replicated and remodeled from a post-meiotic state to one in which transcription is repressed by chromatin structure in a manner that can be relieved by cell-specific enhancers at appropriate times during development.
在小鼠中，第一轮DNA复制发生在受精卵（1细胞胚胎）中，而合子基因转录大约在受精后20小时开始，这个时间通常与2细胞胚胎的形成相吻合。研究控制这些发育调控事件机制的一种方法是将质粒DNA显微注射到小鼠卵母细胞和胚胎的细胞核中，以确定调控转录和复制的独特DNA序列的需求。这些研究和其他研究的结果揭示了两种调控动物发育起始的重要机制。第一种是一个细节未知的时间依赖性“合子钟”，它会延迟转录的起始，无论是否形成2细胞胚胎。第二种机制是，它会特异性地抑制卵母细胞和1细胞胚胎的母源原核以及2细胞胚胎的所有细胞核（无论其亲本来源或倍性如何）中启动子和复制起点的活性。这种抑制与染色质有关，但用特定的胚胎反应性增强子解除这种抑制的显著能力首先出现在2细胞胚胎形成时。当细胞分化变得明显时，介导增强子对启动子活性刺激所需的TATA框出现得更晚。因此，生物钟会延迟转录，直到父源和母源基因组都被复制并从减数分裂后的状态重塑为一种在发育过程中的适当时间可以被细胞特异性增强子解除染色质结构抑制转录的状态。
