Nature：受精卵前期发育重要机制难题被解开

　　

生物通报道，纽约大学生物系，犹他州大学人类遗传研究所以果蝇为模型，在受精卵早期发育的控制机制的研究上取得新的进展，相关的成果公布在新一期（11月20）的Nature上。

 

在生物界，所有动物在胚胎发育的起始阶段都受到母体基因表达产物的调控，这一基因产物在卵母细胞时期就已经产生。一旦卵细胞受精成为合子后，进入胚胎发育的另一个阶段后，母体基因产物就会交出权利，转由受精卵的基因组来调控胚胎的发育。

 

在转交后，很多的母体RNAs会降解或是转录成合子RNAs ensues。长期以来，科学家们都质疑，在这个转接的过程中又有哪些因子起调控作用。

最新的研究发现，microRNA和Smaug介导的母体RNA降解过程中的产物可能是起调控作用的一些因子。尽管，转录因子激活合子基因组的机制暂时不明。但是，新的研究发现，果蝇早期发育过程中很多的转录基因都具有相同的序列结构，cis-regulatory heptamer motif，CAGGTAG和相关的序列，这些结构都与TAGteam位点作用，TAGteam是专注于转录因子功能的序列。

 

在本研究中，研究者发现果蝇的锌指蛋白Zelda（Zld；Zinc-finger early Drosophila activator）可与上述的序列特殊的位点结合，通过瞬间转染分析研究者发现结合后可激发转录活性。如果果蝇的胚胎发生突变，Zld缺失，将导致囊胚层无法发育，并且会影响多种关键基因的表达活性，影响胚胎发育的发生。

 

对胚胎发育进行全面的分析发现，Zld对早期合子基因组具有重要的影响意义，而且在母体RNAs调控机制转向合子基因组调控机制的过程中，Zld也具有重要的调控意义。

 

原文摘要：The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila

 

【Abstract】

In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal-to-zygotic transition. During this time, many maternal RNAs are degraded and transcription of zygotic RNAs ensues1. There is a long-standing question as to which factors regulate these events. The recent findings that microRNAs2, 3 and Smaug4 mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genome remain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences5, 6, collectively referred to as TAGteam sites5 raised the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc-finger protein Zelda (Zld; Zinc-finger early Drosophila activator) binds specifically to these sites and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination and pattern formation. Global expression profiling confirmed that Zld has an important role in the activation of the early zygotic genome and suggests that Zld may also regulate maternal RNA degradation during the maternal-to-zygotic transition.

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