Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.
Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.
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发表时间：
1998-10
期刊：
影响因子：
4.6
通讯作者：
A. Duggan;C. Ma;M. Chalfie
中科院分区：
文献类型：
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作者：
A. Duggan;C. Ma;M. Chalfie
秀丽隐杆线虫拥有六个形态相似的神经元，负责感知身体的轻轻触摸。以前的遗传学研究确定了这些触觉细胞的产生和分化所必需的基因。特别地，unc-86编码产生触摸细胞所需的POU型同源结构域蛋白，而mec-3编码触摸细胞分化所需的LIM型同源结构域蛋白。分子生物学研究表明MEC-3和mec-86可以协同结合到mec-3启动子中的位点上，并在体外协同激活其转录。在这里，我们发现，在mec-3的两个假定的目标，mec-4和mec-7基因，这是必要的触摸细胞的功能的启动子中也发现了mec-86：：MEC-3异源寡聚体结合位点。这些位点在相关线虫C. briggsae是启动子活性所必需的。当其中一个结合位点被克隆到异源启动子中时，在触觉细胞和两到四个表达mec-3和unc-86的其他细胞中发现表达。这些数据支持一个模型，其中触摸细胞分化指定，部分，由β-86：：MEC-3异源寡聚体，而不是由MEC-3单独。由热休克启动子驱动的mec-3的异位表达也支持这一假设：在这些条件下，几个额外的细胞获得接触细胞的特征需要unc-86。由于接触细胞谱系在MEC-3之前表达β-86，MEC-3似乎修饰β-86的活性，导致接触细胞特异性基因表达。由于MEC-86和MEC-3都具有激活结构域，因此异源寡聚体的形成可以产生强激活剂。在触觉细胞中MEC-3对E10 -86功能的修饰中，这些研究提供了一个例子，说明转录因子的顺序激活如何决定特定细胞谱系中的细胞命运。
The nematode Caenorhabditis elegans possesses six morphologically similar neurons that are responsible for sensing gentle touch to the body. Previous genetic studies identified genes that are necessary for the production and differentiation of these touch cells. In particular, unc-86 encodes a POU-type homeodomain protein needed for the production of the touch cells, while mec-3 encodes a LIM-type homeodomain protein needed for the differentiation of the touch cells. Molecular studies showed that MEC-3 and UNC-86 bind cooperatively to sites in the mec-3 promoter and can synergistically activate transcription from it in vitro. Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells. These sites, which are well-conserved in the related nematode C. briggsae, are required for promoter activity. When one of the binding sites is cloned into a heterologous promoter, expression is found in the touch cells and two to four other cells that express mec-3 and unc-86. These data support a model in which touch-cell differentiation is specified, in part, by the UNC-86::MEC-3 hetero-oligomer and not by MEC-3 alone. Ectopic expression of mec-3, driven by a heat-shock promoter, also supports this hypothesis: the acquisition of touch-cell characteristics by several additional cells under these conditions required unc-86. Since the touch-cell lineages express UNC-86 before MEC-3, MEC-3 appears to modify the activity of UNC-86, leading to touch-cell-specific gene expression. Because both UNC-86 and MEC-3 have activation domains, the formation of the hetero-oligomer may create a strong activator. In the modification of UNC-86 function by MEC-3 in the touch cells, these studies provide an example of how the sequential activation of transcription factors can determine cell fate within particular cell lineages.