title: Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification.
abstract: The cell-fate specification of the anchor cell (AC) and a ventral uterine precursor cell (VU) in Caenorhabditis elegans is initiated by a stochastic interaction between LIN-12/Notch receptor and LAG-2/Delta ligand in two neighboring Z1.ppp and Z4.aaa cells. Both cells express lin-12 and lag-2 before specification, and a small difference in LIN-12 activity leads to the exclusive expressions of lin-12 in VU and lag-2 in the AC, through a feedback mechanism of unknown nature. Here we show that the expression pattern of lag-1/CSL, a transcriptional repressor itself that turns into an activator upon binding of the intracellular domain of Notch, overlaps with that of lin-12. Site-directed mutagenesis of LAG-1 binding sites in lag-1 maintains its expression in the AC, and eliminates it in the VU. Thus, AC/VU cell-fate specification appears to involve direct regulation of lag-1 expression by the LAG-1 protein, activating its transcription in VU cells, but repressing it in the AC.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Vit Na
authors.initials: VN
authors.lastname: Choi
authors.forename: Seong Kyun
authors.initials: SK
authors.lastname: Park
authors.forename: Byung Joon
authors.initials: BJ
authors.lastname: Hwang
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D051880:Receptors, Notch