Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization

Autoři: Leslie Dunipace aff001;  Zsuzsa Ákos aff001;  Angelike Stathopoulos aff001
Působiště autorů: California Institute of Technology, Pasadena, CA aff001
Vyšlo v časopise: Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008525
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008525


Developmental genes are often regulated by multiple enhancers exhibiting similar spatiotemporal outputs, which are generally considered redundantly acting though few have been studied functionally. Using CRISPR-Cas9, we created deletions of two enhancers, brk5’ and brk3’, that drive similar but not identical expression of the gene brinker (brk) in early Drosophila embryos. Utilizing both in situ hybridization and quantitative mRNA analysis, we investigated the changes in the gene network state caused by the removal of one or both of the early acting enhancers. brk5’ deletion generally phenocopied the gene mutant, including expansion of the BMP ligand decapentaplegic (dpp) as well as inducing variability in amnioserosa tissue cell number suggesting a loss of canalization. In contrast, brk3’ deletion presented unique phenotypes including dorsal expansion of several ventrally expressed genes and a decrease in amnioserosa cell number. Similarly, deletions were made for two enhancers associated with the gene short-gastrulation (sog), and sog.dist, demonstrating that they also exhibit distinct patterning phenotypes and affect canalization. In summary, this study shows that similar gene expression driven by coacting enhancers can support distinct, and sometimes complementary, functions within gene regulatory networks and, moreover, that phenotypes associated with individual enhancer deletion mutants can provide insight into new gene functions.

Klíčová slova:

BMP signaling – Drosophila melanogaster – Embryos – Gene expression – Gene regulation – Gene regulatory networks – Genetic loci – Phenotypes


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