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Pré-Publication, Document De Travail Année : 2023

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

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

Résumé

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.

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Génétique
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Dates et versions

hal-04252150 , version 1 (20-10-2023)

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Maximilian Fitz-James, Gonzalo Sabarís, Peter Sarkies, Frédéric Bantignies, Giacomo Cavalli. Interchromosomal contacts between regulatory regions trigger stable transgenerational epigenetic inheritance in Drosophila. 2023. ⟨hal-04252150⟩
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