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Nat Genet. 2017 Jun;49(6):876-886. doi: 10.1038/ng.3848. Epub 2017 Apr 24.

Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila.

Author information

1
Institute of Human Genetics, UMR 9002, CNRS and University of Montpellier, Montpellier, France.
2
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
3
CBGP-INRA, Montferrier sur Lez, France.
4
Division of Biology, California Institute of Technology, Pasadena, California, USA.
5
Unité de Mathématiques et Informatique Appliquées de Toulouse, INRA, Castanet Tolosan, France.
6
Faculty of Science, University of Basel, Basel, Switzerland.

Abstract

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.

PMID:
28436983
PMCID:
PMC5484582
DOI:
10.1038/ng.3848
[Indexed for MEDLINE]
Free PMC Article

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