title: Multiple Promoter Targeting Sequences exist in Abdominal-B to regulate long-range gene activation.
abstract: In complex genomes, insulators set up chromatin domain boundaries and protect promoters from inappropriate activation by enhancers from neighboring genes. The Drosophila Abdominal-B locus uses insulator elements to organize its large regulatory region into several body segment-specific chromatin domains. This organization leads to a problem in enhancer-promoter communication, that is, how do distal enhancers activate the Abd-B promoter when there are several insulators in between? This issue is partially resolved by the Promoter Targeting Sequence, which can overcome the enhancer blocking effect of an insulator. In this study, we describe a new Promoter Targeting Sequence, PTS-6, from the Abd-B 3' regulatory region. PTS-6, comprised of approximately 200 bp, was found to bypass both homologous Abdominal-B insulators, such as Fab-7 and Fab-8, and a heterologous insulator, suHw. Most importantly, it also overcomes a combination of two insulators such as Fab-7/Fab-8. Thus, PTS-6 could, in principle, target remote enhancers that are separated from the Abd-B promoter by multiple insulators. In addition, PTS-6 selectively targets the distal enhancer to only one transgenic promoter, and it strongly facilitates Abd-B enhancers. These results suggest that promoter targeting is necessary for long-range enhancer-promoter communication in Abd-B, and PTS elements could be a common occurrence in large, complex genetic loci.
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Sheryl
authors.initials: S
authors.lastname: Smith
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Jumin
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D049750:Genome, Insect; D018398:Homeodomain Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: C062393:Abd-B proteins, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins