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

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Fitz-James, Maximilian | Sabarís, Gonzalo | Sarkies, Peter | Bantignies, Frédéric | Cavalli, Giacomo

Edité par CCSD ; Cell Press -

International audience. Non-genetic information can be inherited across generations in a process known as Transgenerational Epigenetic Inheritance (TEI). 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. Here, by mutating transcription factor binding sites within the Fab-7 element, we demonstrate the importance of the proteins Pleiohomeotic and GAGA-factor in the establishment and maintenance of TEI. 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, respectively. Using an in vivo synthetic biology system to induce them, we then show that chromatin contacts alone can establish TEI, providing a mechanism by which hemizygosity of one locus can establish epigenetic memory at another distant locus in trans through chromatin contacts.

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