The CSL transcription factor LAG-1 directly represses hlh-6 expression in C. elegans.
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.
Ghai
Vikas
V
Genes and Development Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Gaudet
Jeb
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D007814:Larva; D009154:Mutation; D009928:Organ Specificity; D010614:Pharynx / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D015398:Signal Transduction
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051880:Receptors, Notch; C517649:HLH-6 protein, C elegans; C099355:LAG-1 protein, C elegans