Project description:Transgenerational epigenetic inheritance entails transmission of epigenetically determined phenotypic traits through multiple generations. However, very little is known on the principles and the mechanisms governing this type of inheritance. Here, we established stable and isogenic Drosophila epilines by transiently enhancing long-range chromatin interactions. Such epilines display two opposing chromatin states, which depend on differential levels of the H3K27me3 histone mark. Once established, both the active and the repressed epialleles can dominantly be transmitted to naïve flies and can induce paramutation. Importantly, both epilines can be reset to an intermediate naïve state by disrupting chromatin interactions. Finally, we show that the environment can modulate the expressivity of the epialleles and we extend our paradigm to naturally occurring genetic makeups. Our work sheds light on how nuclear organization contributes to epigenetically heritable phenotypic variability and therefore to evolution.
Project description:The notion that genes are the sole units of heredity and that a barrier exists between soma and germline has been a major hurdle in elucidating the heritability of traits that were observed to follow a non-Mendelian inheritance pattern. It was only after the conception of “epigenetics” by C. H. Waddington that the effect of parental environment on subsequent generations via non-DNA sequence-based mechanisms, such as DNA methylation, chromatin modifications, non-coding RNAs and proteins, could be established in various organisms, now referred to as multigenerational epigenetic inheritance. Despite the growing body of evidence, the male gamete-derived epigenetic factors that mediate the transmission of such phenotypes are seldom explored, particularly in the model organism Drosophila melanogaster. Using the heat stress-induced multigenerational epigenetic inheritance paradigm in a widely used position-effect variegation line of Drosophila, named white-mottled, we have dissected the effect of heat stress on the sperm proteome in the current study. We demonstrate that multiple successive generations of heat stress at the early embryonic stage results in a significant downregulation of proteins associated with translation, chromatin organization, microtubule-based processes, and generation of metabolites and energy in the Drosophila sperms. Based on our findings, we propose chromatin-based epigenetic mechanisms, a well-established mechanism for environmentally induced multigenerational effects, as a plausible way of transmitting heat stress memory via the male germ line in subsequent generations. Moreover, we demonstrate the effect of multiple generations of heat stress on the reproductive fitness of Drosophila, shedding light on the adaptive or maladaptive potential of heat stress-induced multigenerational phenotypes.
Project description:Drosophila Haspin kinase phosphorylates Histone H3 at threonine 3 at centromeric heterochromatin and either lamin- or polycomb-enriched euchromatic regions, being required for nuclear organization of interphase cells and polycomb-dependent gene silencing.
Project description:Polycomb repressive complex 2-dependent and –independent functions of Jarid2 in transcriptional regulation in Drosophila [Affymetrix]
Project description:Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila [ChIP-Seq]