title: Disruption of the abdominal-B promoter tethering element results in a loss of long-range enhancer-directed Hox gene expression in Drosophila.
abstract: There are many examples within gene complexes of transcriptional enhancers interacting with only a subset of target promoters. A number of molecular mechanisms including promoter competition, insulators and chromatin looping are thought to play a role in regulating these interactions. At the Drosophila bithorax complex (BX-C), the IAB5 enhancer specifically drives gene expression only from the Abdominal-B (Abd-B) promoter, even though the enhancer and promoter are 55 kb apart and are separated by at least three insulators. In previous studies, we discovered that a 255 bp cis-regulatory module, the promoter tethering element (PTE), located 5' of the Abd-B transcriptional start site is able to tether IAB5 to the Abd-B promoter in transgenic embryo assays. In this study we examine the functional role of the PTE at the endogenous BX-C using transposon-mediated mutagenesis. Disruption of the PTE by P element insertion results in a loss of enhancer-directed Abd-B expression during embryonic development and a homeotic transformation of abdominal segments. A partial deletion of the PTE and neighboring upstream genomic sequences by imprecise excision of the P element also results in a similar loss of Abd-B expression in embryos. These results demonstrate that the PTE is an essential component of the regulatory network at the BX-C and is required in vivo to mediate specific long-range enhancer-promoter interactions.
authors.affiliation: Biology Department, Harvey Mudd College, Claremont, California, United States of America.
authors.forename: Margaret C W
authors.initials: MC
authors.lastname: Ho
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Schiller
authors.forename: Omar S
authors.initials: OS
authors.lastname: Akbari
authors.forename: Esther
authors.initials: E
authors.lastname: Bae
authors.forename: Robert A
authors.initials: RA
authors.lastname: Drewell
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
chemical_list: D018398:Homeodomain Proteins