Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila
Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila
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DOI：
10.1073/pnas.0506462102
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发表时间：
2005-09-13
影响因子：
11.1
通讯作者：
Hanes, SD
中科院分区：
文献类型：
--
作者：
Lebrecht, D;Foehr, M;Hanes, SD
DNA结合蛋白的协同相互作用与多种生物体的细胞命运决定有关。然而，迄今为止，很少有这样的相互作用的重要性已经明确在体内测试的例子。在这里，我们测试的重要性，合作DNA结合的Bicoid蛋白在建立一个模式沿着的前，后轴的早期果蝇胚胎。我们发现，bicoid突变体在合作DNA结合方面有缺陷，无法指导头部和胸部的正常发育，导致胚胎死亡。突变体不能忠实地刺激下游靶基因如hunchback（hb）、giant和Kruppel的转录。体内基因表达的定量分析表明，bcd协同突变体不能准确地指导hb沿前后轴沿着表达的程度，并且显示出产生hb基因表达的急剧开/关转换的能力降低。这些在精确转录控制中的失败证明了合作DNA结合对体内胚胎图案形成的重要性。
Cooperative interactions by DNA-binding proteins have been implicated in cell-fate decisions in a variety of organisms. To date, however, there are few examples in which the importance of such interactions has been explicitly tested in vivo. Here, we tested the importance of cooperative DNA binding by the Bicoid protein in establishing a pattern along the anterior-posterior axis of the early Drosophila embryo. We found that bicoid mutants specifically defective in cooperative DNA binding fail to direct proper development of the head and thorax, leading to embryonic lethality. The mutants did not faithfully stimulate transcription of downstream target genes such as hunchback (hb), giant, and Kruppel. Quantitative analysis of gene expression in vivo indicated that bcd cooperativity mutants were unable to accurately direct the extent to which hb is expressed along the anterior-posterior axis and displayed a reduced ability to generate sharp on/off transitions for hb gene expression. These failures in precise transcriptional control demonstrate the importance of cooperative DNA binding for embryonic patterning in vivo.