Journal
NATURE GENETICS
Volume 49, Issue 6, Pages 876-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3848
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Funding
- Fondation pour la Recherche Medicale (FRM)
- CNRS
- ETH Zurich
- Sir Henry Wellcome Postdoctoral Fellowship [WT100136MA]
- FP7 European Network of Excellence EpiGeneSys
- Swiss National Science Foundation
- NIH [GM097363]
- European Research Council [232947]
- European Union [676556]
- Agence Nationale de la Recherche
- Fondation pour la Recherche Medicale
- INSERM
- French National Cancer Institute (INCa)
- Laboratory of Excellence EpiGenMed
- European Research Council (ERC) [232947] Funding Source: European Research Council (ERC)
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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.
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