title: Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans.
abstract: In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorhabditis elegans. We hypothesize that the effect of multiple X-box motifs is not a simple summation of binding effect to individual X-box motifs located within a same gene. To test this hypothesis, we identified eight C. elegans genes that contain two or more X-box motifs using comparative genomics. We examined one of these genes, F25B4.2, which contains two 15-bp X-box motifs. F25B4.2 expression in ciliated neurons is driven by the proximal motif and its expression is repressed by the distal motif. Our data suggest that two X-box motifs cooperate together to regulate the expression of F25B4.2 in location and intensity. We propose that multiple X-box motifs might be required to tune specific expression level. Our identification of genes with multiple X-box motifs will also improve our understanding of RFX/DAF-19-mediated regulation in C. elegans and in other organisms including humans.
authors: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
authors: Jeffery S C
authors: JS
authors: Chu
authors: Maja
authors: M
authors: Tarailo-Graovac
authors: Di
authors: D
authors: Zhang
authors: Jun
authors: J
authors: Wang
authors: Bora
authors: B
authors: Uyar
authors: Domena
authors: D
authors: Tu
authors: Joanne
authors: J
authors: Trinh
authors: David L
authors: DL
authors: Baillie
authors: Nansheng
authors: N
authors: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D023281:Genomics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C410596:DAF-19 protein, C elegans; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C570296:peli-1 protein, C elegans