Boundaries mediate long-distance interactions between enhancers and promoters in the Drosophila Bithorax complex.

TitleBoundaries mediate long-distance interactions between enhancers and promoters in the Drosophila Bithorax complex.
Publication TypeJournal Article
Year of Publication2018
AuthorsPostika, N, Metzler, M, Affolter, M, Müller, M, Schedl, P, Georgiev, P, Kyrchanova, O
JournalPLoS Genet
Volume14
Issue12
Paginatione1007702
Date Published2018 12
ISSN1553-7404
KeywordsAnimals, Animals, Genetically Modified, Drosophila melanogaster, Drosophila Proteins, Enhancer Elements, Genetic, Female, Genes, Homeobox, Genes, Insect, Homeodomain Proteins, Insulator Elements, Male, Models, Genetic, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors
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.

DOI10.1371/journal.pgen.1007702
Alternate JournalPLoS Genet.
PubMed ID30540750
PubMed Central IDPMC6306242
Grant ListR35 GM126975 / GM / NIGMS NIH HHS / United States