Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes.

Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes.
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DOI:
10.1016/j.ydbio.2010.06.026
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发表时间:
2010-09-15
影响因子:
2.7
通讯作者:
Cline TW
Cline TW
中科院分区:
生物学3区
文献类型:
--
作者:
Harrison MM;Botchan MR;Cline TW

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母体贡献的mrna和蛋白质控制受精后的初始发育阶段。在此期间,大部分合子基因组保持转录沉默。广泛合子转录的开始与母体提供的mrna在母体到合子转化(MZT)中的降解相协调。虽然大多数基因组在MZT之前沉默,但对生物体未来发育至关重要的一小部分合子基因被转录。在我们的实验室和其他人之前的工作中发现了TAGteam元件,这是一组相关的七聚体dna序列,位于许多早期表达的果蝇基因的启动子中,这些启动子需要驱动它们异常的早期转录。为了了解这一独特的基因子集是如何被调控的,我们确定了一个tagteam结合因子Grainyhead (Grh)。我们证明了Grh和之前表征的转录激活子Zelda (Zld)以不同的亲和力结合到不同的TAGteam序列上,并且Grh与Zld竞争TAGteam占用。此外,Grh在胚胎早期的过度表达会导致细胞分裂缺陷,表型上表现为Zld耗竭。我们的研究结果表明,在胚胎早期发育过程中,基因表达的精确时间由启动子中TAGteam元件的序列和转录因子Grh和Zld的相对水平共同调控。
Maternally contributed mRNAs and proteins control the initial stages of development following fertilization. During this time, most of the zygotic genome remains transcriptionally silent. The initiation of widespread zygotic transcription is coordinated with the degradation of maternally provided mRNAs at the maternal-to-zygotic transition (MZT). While most of the genome is silenced prior to the MZT, a small subset of zygotic genes essential for the future development of the organism is transcribed. Previous work in our laboratory and others identified the TAGteam element, a set of related heptameric DNA-sequences in the promoters of many early-expressed Drosophila genes required to drive their unusually early transcription. To understand how this unique subset of genes is regulated, we identified a TAGteam-binding factor Grainyhead (Grh). We demonstrated that Grh and the previously characterized transcriptional activator Zelda (Zld) bind to different TAGteam sequences with varying affinities, and that Grh competes with Zld for TAGteam occupancy. Moreover, overexpression of Grh in the early embryo causes defects in cell division, phenocopying Zld depletion. Our findings indicate that during early embryonic development the precise timing of gene expression is regulated by both the sequence of the TAGteam elements in the promoter and the relative levels of the transcription factors Grh and Zld.
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