Ghai Vikas, Gaudet Jeb
Genes and Development Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Dev Biol. 2008 Oct 15;322(2):334-44. doi: 10.1016/j.ydbio.2008.07.018. Epub 2008 Jul 25.
The Caenorhabditis elegans gene hlh-6 is expressed specifically in pharyngeal glands, one of five distinct pharyngeal cell types. Expression of hlh-6 is controlled by a discrete set of cis-regulatory elements, including a negative element called HRL1. Here we demonstrate that HRL1 is a functional binding site for LAG-1, the CSL transcriptional effector of Notch in C. elegans, and that regulation of hlh-6 by LAG-1 is direct. Regulation of hlh-6 by LAG-1 is strictly negative: removal of HRL1 or LAG-1 regulation results in ectopic expression of hlh-6, but does not affect expression in pharyngeal glands. Furthermore, direct regulation of hlh-6 expression does not appear to involve Notch signaling, contrary to the canonical mechanism by which CSL factors regulate target genes. We also identify an additional cis-regulatory element in the hlh-6 promoter that, together with previously identified elements, is sufficient to overcome repression by LAG-1 and activate hlh-6 expression in pharyngeal glands.
秀丽隐杆线虫基因hlh-6特异性地在咽腺中表达，咽腺是五种不同的咽细胞类型之一。hlh-6的表达受一组离散的顺式调控元件控制，包括一个名为HRL1的负调控元件。在此我们证明，HRL1是秀丽隐杆线虫中Notch的CSL转录效应因子LAG-1的功能性结合位点，并且LAG-1对hlh-6的调控是直接的。LAG-1对hlh-6的调控严格呈负性：去除HRL1或LAG-1的调控会导致hlh-6的异位表达，但不影响其在咽腺中的表达。此外，与CSL因子调控靶基因的经典机制相反，hlh-6表达的直接调控似乎不涉及Notch信号传导。我们还在hlh-6启动子中鉴定出另一个顺式调控元件，该元件与先前鉴定的元件一起，足以克服LAG-1的抑制作用并激活hlh-6在咽腺中的表达。
