Raharjo Indra, Gaudet Jeb
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Dev Biol. 2007 Feb 1;302(1):295-308. doi: 10.1016/j.ydbio.2006.09.036. Epub 2006 Sep 26.
The pharyngeal glands of Caenorhabditis elegans are one of five cell types in the pharynx. The transcription factor HLH-6 is required for gland development and function, and is specifically expressed in pharyngeal glands. As a first step to understanding specification of pharyngeal glands, we analyzed the promoter of hlh-6 to identify the elements required for gland-specific expression. Our experiments identified three distinct regulatory elements required for hlh-6 expression: a PHA-4-binding site and two new elements, HRL1 and HRL2 (for hlh-6 regulatory elements 1 and 2). The three elements employ a simple logic for producing cell-type-specific expression: the PHA-4 site restricts expression to the pharynx, HRL2 restricts expression in both a position and lineage-dependent manner, and HRL1 restricts expression to a subset of cell types. In isolation, these three elements have little or no enhancer activity but in combination they produce robust, gland-specific expression. These findings describe a combinatorial code for gland-specific expression and suggest that similar codes may be employed for specification of other pharyngeal cell types.
秀丽隐杆线虫的咽腺是咽部五种细胞类型之一。转录因子HLH-6是腺体发育和功能所必需的，并且在咽腺中特异性表达。作为理解咽腺特化的第一步，我们分析了hlh-6的启动子以鉴定腺体特异性表达所需的元件。我们的实验确定了hlh-6表达所需的三个不同调控元件：一个PHA-4结合位点以及两个新元件HRL1和HRL2（分别代表hlh-6调控元件1和2）。这三个元件采用一种简单逻辑来产生细胞类型特异性表达：PHA-4位点将表达限制在咽部，HRL2以位置和谱系依赖的方式限制表达，而HRL1将表达限制在细胞类型的一个子集中。单独来看，这三个元件几乎没有或没有增强子活性，但组合在一起时它们会产生强大的、腺体特异性的表达。这些发现描述了一种腺体特异性表达的组合密码，并表明类似的密码可能用于其他咽部细胞类型的特化。
