# Promoter competition and Polycomb response elements govern transvection efficiency between co-regulated engrailed and invected genes in Drosophila

## TL;DR

This paper explores how gene regulation occurs between paired chromosomes in fruit flies, revealing how promoters and enhancers interact to control gene activity.

## Contribution

The study identifies promoter competition and Polycomb response elements as key regulators of transvection efficiency between co-regulated genes.

## Key findings

- The en promoter in cis prevents trans-activation of inv, but its removal enables robust transvection.
- Polycomb response elements enhance transvection reliability but are not essential for trans-activation.
- Transvection at the en-inv locus is developmentally regulated and can be reconstituted in transgenic constructs.

## Abstract

Transvection is a phenomenon where gene regulatory elements interact between different chromosomes, adding an additional layer of regulatory control beyond traditional cis-interactions. Although transvection effects have been characterized for many individual genes in Drosophila, it remains unclear how trans-interactions occur among multiple co-regulated genes where enhancers are shared. Here we demonstrate that transvection is supported at the engrailed-invected (en-inv) locus, where transcription of the two developmental genes is coordinated by common enhancers. Our data show that the presence of the en promoter in cis to the enhancers prevents trans-activation of inv, but removal of this promoter enables robust transvection, demonstrating competition between heterologous promoters in trans. We also find that local Polycomb response elements (PREs) enhance transvection reliability but are not strictly required for trans-activation. Furthermore, our analysis reveals that transvection at this locus is developmentally regulated, occurring efficiently in third instar larval tissues and late-stage embryos but not in early embryonic stages. Finally, we show that en-inv transvection can be reconstituted using transgenic constructs at an ectopic chromosomal location, where it produces a striking reciprocal expression pattern between en in cis and inv in trans, suggesting that these enhancers can choose to activate one promoter or the other in a stochastic manner.

Transvection (or trans-activation) is a process whereby an enhancer on one chromosome activates the promoter of a gene on a paired homologous chromosome. Many duplicated developmental genes in Drosophila are co-activated by shared enhancers in cis, which can be facilitated by interactions between promoter-proximal elements. Could co-activation also occur in trans when the two promoters are on paired homologs? Contrary to Cheng et al.’s expectations, the engrailed enhancers that normally activate two promoters in cis could act in trans only when a cis-promoter was removed. Furthermore, promoter proximal elements facilitate expression in trans, but are not strictly required for trans-activation.