Keywords: j. pairing/transvection; p. cis-regulatory logic
DNA elements act across long genomic distances to regulate gene expression in processes including enhancer-promoter interactions and genetic imprinting. During the gene-regulatory phenomenon of transvection in Drosophila, DNA elements on one allele of a gene act between chromosomes to increase or decrease expression of another allele of the gene. Despite the discovery of transvection over 60 years ago, little is known about its biological role. Furthermore, how separable DNA elements contribute to activating or repressing transvection at distinct times during development is unclear. Here, we study the expression of spineless (ss) in the developing fly eye as a paradigm to understand gene activation and repression between chromosomes. We found a biological role for transvection in controlling the stochastic expression of naturally occurring ss alleles. We characterized CRISPR engineered deletions of sequences across the ss locus and identified DNA elements required for activating and repressing transvection. We found that enhancers participate in transvection at distinct times in development to promote gene expression. Finally, bringing a silencer element on a different chromosome into proximity with the ss locus “reconstitutes” the gene, leading to repression.Our studies show that transvection regulates gene expression via distinct DNA elements at specific timepoints in development with implications for genome architecture.