Boundaries mediate long-distance interactions between enhancers and promoters in the Drosophila Bithorax complex. Author Nikolay Postika, Mario Metzler, Markus Affolter, Martin Müller, Paul Schedl, Pavel Georgiev, Olga Kyrchanova Publication Year 2018 Type Journal Article Abstract Drosophila bithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes, Ubx, abd-A, and Abd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which function to block crosstalk between adjacent domains, ensuring that they can act autonomously. Paradoxically, seven of the BX-C regulatory domains are separated from their gene target by at least one boundary, and must "jump over" the intervening boundaries. To understand the jumping mechanism, the Mcp boundary was replaced with Fab-7 and Fab-8. Mcp is located between the iab-4 and iab-5 domains, and defines the border between the set of regulatory domains controlling abd-A and Abd-B. When Mcp is replaced by Fab-7 or Fab-8, they direct the iab-4 domain (which regulates abd-A) to inappropriately activate Abd-B in abdominal segment A4. For the Fab-8 replacement, ectopic induction was only observed when it was inserted in the same orientation as the endogenous Fab-8 boundary. A similar orientation dependence for bypass activity was observed when Fab-7 was replaced by Fab-8. Thus, boundaries perform two opposite functions in the context of BX-C-they block crosstalk between neighboring regulatory domains, but at the same time actively facilitate long distance communication between the regulatory domains and their respective target genes. Keywords Animals, Drosophila Proteins, Promoter Regions, Genetic, Nuclear Proteins, Transcription Factors, Mutation, Models, Genetic, Animals, Genetically Modified, Female, Male, Drosophila melanogaster, Insulator Elements, Homeodomain Proteins, Enhancer Elements, Genetic, Regulatory Sequences, Nucleic Acid, Genes, Insect, Genes, Homeobox Journal PLoS Genet Volume 14 Issue 12 Pages e1007702 Date Published 2018 Dec ISSN Number 1553-7404 DOI 10.1371/journal.pgen.1007702 Alternate Journal PLoS Genet PMCID PMC6306242 PMID 30540750 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML