Coupling of Enhancer and Insulator Properties Identified in Two Retrotransposons Modulates Their Mutagenic Impact on Nearby Genes

Abstract

ABSTRACT We recently reported a novel transposition system in which two retroelements from Drosophila melanogaster , ZAM and Idefix , are highly mobilized and preferentially insert within intergenic regions. Among the loci where new copies are detected, a hot spot for their insertion was identified at the white locus, where up to three elements occurred within a 3-kb fragment upstream of the transcriptional start site of white . We have used these insertions as molecular entry points to throw light on the mutagenic effect exerted by multiple insertions of retrotransposons within intergenic regions of a genome. Analysis of the molecular mechanisms by which ZAM and Idefix elements interfere with the regulation of the white gene has shown that ZAM bears cis -acting regulatory sequences able to enhance transcription of the white gene in the eyes of the flies. This activation may be counteracted by Idefix , which acts as an insulator able to isolate the white gene from the upstream ZAM enhancer. In addition to revealing a novel insulator sequence with its own specific features, our data clearly illustrate how retroelements can act as epigenetic factors able to interfere with the transcriptional regulation of their host.