The open for business model of the bithorax complex in Drosophila.
The open for business model of the bithorax complex in Drosophila.
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DOI：
10.1007/s00412-015-0522-0
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发表时间：
2015-09
期刊：
影响因子：
1.6
通讯作者：
Karch F
中科院分区：
文献类型：
--
作者：
Maeda RK;Karch F
经过近30年的努力，艾德刘易斯在1978年发表了他的里程碑式的论文，其中他描述了一系列突变的分析，这些突变影响了沿着果蝇前后（AP）轴形成的片段的身份（刘易斯1978）。这些突变在互补测试中表现出非典型的方式，形成了艾德刘易斯所谓的“假等位基因”系列。正因为如此，他从未想过这些突变代表了片段特异性基因。由于所有这些突变都集中在果蝇第三条染色体的一个特定区域，该位点被称为双胸复合体（BX-C）。刘易斯的文章的一个关键发现是，它首次向广大的科学观众揭示了染色体沿着特定片段突变的顺序与它们影响的AP轴沿着的片段顺序之间存在显着的相关性。在艾德·刘易斯看来，他发现的突变体影响了“特定片段功能”，当一个人沿着体轴从前向后移动时，这些功能沿着染色体顺序激活（现在在初级生物学教科书中引用的共线性概念）。当Hogness和Bender实验室在20世纪80年代中期通过开创性的染色体步移克隆BX-C时，“片段特异性功能”的性质开始变得清晰（Bender等人，1983 a; Karch等人，1985）。通过这种分子生物学的努力，以及沿着马德里的Gines Morata小组（Sanchez-Herrero et al. 1985）和苏塞克斯的Robert Whittle小组（Tiong et al. 1985）进行的遗传表征，很快就清楚了整个BX-C只编码三种蛋白质编码基因（Ubx、abd-A和abd-B）。后来，针对Ubx蛋白的免疫染色暗示，片段特异性功能实际上可能是调节三种蛋白编码基因表达的顺式调节元件。1987年，Peifer、Karch和Bender提出了BX-C功能的综合模型，其中“片段特异性功能”表现为调节Ubx、abd-A或Abd-B的片段特异性增强子（Peifer et al. 1987）。他们的模型的关键是，这些增强子的片段地址不是增强子本身的固有能力，而是由它们所在的染色体位置决定的。在他们看来，片段特异性功能的顺序激活是由于染色质结构域沿着从前向后移动时顺序打开所致。这种模式很快被称为开放的商业模式。虽然开放的商业模式很容易在概念层面上可视化，但近30年来一直缺少验证这种模式的分子证据。最近的出版物描述了Bender和金斯顿实验室的杰出联合努力，现在提供了支持该模型的缺失证据（Bowman等人，2014）。本文的目的是回顾开放的商业模式，并带读者通过遗传参数，导致其阐述。
After nearly 30 years of effort, Ed Lewis published his 1978 landmark paper in which he described the analysis of a series of mutations that affect the identity of the segments that form along the anterior-posterior (AP) axis of the fly (Lewis 1978). The mutations behaved in a non-canonical fashion in complementation tests, forming what Ed Lewis called a “pseudo-allelic” series. Because of this, he never thought that the mutations represented segment-specific genes. As all of these mutations were grouped to a particular area of the Drosophila third chromosome, the locus became known of as the bithorax complex (BX-C). One of the key findings of Lewis’ article was that it revealed for the first time, to a wide scientific audience, that there was a remarkable correlation between the order of the segment-specific mutations along the chromosome and the order of the segments they affected along the AP axis. In Ed Lewis’ eyes, the mutants he discovered affected “segment-specific functions” that were sequentially activated along the chromosome as one moves from anterior to posterior along the body axis (the colinearity concept now cited in elementary biology textbooks). The nature of the “segment-specific functions” started to become clear when the BX-C was cloned through the pioneering chromosomal walk initiated in the mid 1980s by the Hogness and Bender laboratories (Bender et al. 1983a; Karch et al. 1985). Through this molecular biology effort, and along with genetic characterizations performed by Gines Morata’s group in Madrid (Sanchez-Herrero et al. 1985) and Robert Whittle’s in Sussex (Tiong et al. 1985), it soon became clear that the whole BX-C encoded only three protein-coding genes (Ubx, abd-A, and Abd-B). Later, immunostaining against the Ubx protein hinted that the segment-specific functions could, in fact, be cis-regulatory elements regulating the expression of the three protein-coding genes. In 1987, Peifer, Karch, and Bender proposed a comprehensive model of the functioning of the BX-C, in which the “segment-specific functions” appear as segment-specific enhancers regulating, Ubx, abd-A, or Abd-B (Peifer et al. 1987). Key to their model was that the segmental address of these enhancers was not an inherent ability of the enhancers themselves, but was determined by the chromosomal location in which they lay. In their view, the sequential activation of the segment-specific functions resulted from the sequential opening of chromatin domains along the chromosome as one moves from anterior to posterior. This model soon became known of as the open for business model. While the open for business model is quite easy to visualize at a conceptual level, molecular evidence to validate this model has been missing for almost 30 years. The recent publication describing the outstanding, joint effort from the Bender and Kingston laboratories now provides the missing proof to support this model (Bowman et al. 2014). The purpose of this article is to review the open for business model and take the reader through the genetic arguments that led to its elaboration.