Interchromosomal contacts between regulatory regions trigger stable transgenerational epigenetic inheritance in Drosophila

Abstract

Non-genetic information can be inherited across generations by the process of Transgenerational Epigenetic Inheritance (TEI). TEI can be established by various triggering events, including transient genetic perturbations. In Drosophila, hemizygosity of the Fab-7 regulatory element triggers inheritance of the histone mark H3K27me3 at a homologous locus on another chromosome, resulting in heritable epigenetic differences in eye colour. By mutating transcription factor binding sites within the Fab-7 element, we demonstrate the importance of two proteins in the establishment and maintenance of TEI: GAGA-factor and Pleiohomeotic. We show that these proteins function by recruiting the Polycomb Repressive Complex 2 and by mediating interchromosomal chromatin contacts between Fab-7 and its homologous locus. Finally, using an in vivo synthetic biology system to induce them, we show that chromatin contacts alone can establish TEI, providing a mechanism by which hemizygosity of one locus can establish epigenetic memory at another in trans through long-distance chromatin contacts.