Open AccessStable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila
Author(s) -
Filippo Ciabrelli,
Federico Comoglio,
Simon Fellous,
Boyan Bonev,
Maria Ninova,
Quentin Szabo,
Anne Xuéreb,
Christophe Klopp,
Alexei A. Aravin,
Renato Paro,
Frédéric Bantignies,
Giacomo Cavalli
Publication year - 2017
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/ng.3848
Subject(s) - biology , polycomb group proteins , chromatin , epigenetics , genetics , transgenerational epigenetics , phenotype , histone , prc2 , dna methylation , inheritance (genetic algorithm) , histone h3 , gene , repressor , transcription factor , gene expression
Transgenerational epigenetic inheritance (TEI) describes the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known about the principles and the molecular mechanisms governing this type of inheritance. Here, by transiently enhancing 3D chromatin interactions, we established stable and isogenic Drosophila epilines that carry alternative epialleles, as defined by differential levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming H3K27me3). After being established, epialleles can be dominantly transmitted to naive flies and can induce paramutation. Importantly, epilines can be reset to a naive state by disruption of chromatin interactions. Finally, we found that environmental changes modulate the expressivity of the epialleles, and we extended our paradigm to naturally occurring phenotypes. Our work sheds light on how nuclear organization and Polycomb group (PcG) proteins contribute to epigenetically inheritable phenotypic variability.