Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila.
Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila.
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DOI：
10.1038/ng.3848
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发表时间：
2017-06
期刊：
影响因子：
30.8
通讯作者：
Cavalli G
中科院分区：
文献类型：
--
作者：
Ciabrelli F;Comoglio F;Fellous S;Bonev B;Ninova M;Szabo Q;Xuéreb A;Klopp C;Aravin A;Paro R;Bantignies F;Cavalli G
跨代表观遗传(TEI)研究了在同一基因组DNA序列存在的情况下，不同功能状态在多个世代之间的传递。人们对这种遗传的原理和分子机制知之甚少。在这里，通过瞬时增强3D染色质相互作用，我们建立了稳定和等基因的果蝇外显基因，这些外显基因携带替代的表观等位基因，由多梳依赖的H3K27me3标记的不同水平定义。一旦确定，表观等位基因可以主要传播给幼稚的苍蝇，并诱导辅助肢端。重要的是，外膜可以通过破坏染色质的相互作用而被重置为幼稚状态。最后，我们展示了环境变化可以调节表观等位基因的表达能力，我们将我们的范式扩展到自然发生的表型。我们的工作揭示了核组织和多梳群蛋白如何有助于表观遗传的表型变异。
Transgenerational Epigenetic Inheritance (TEI) studies the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known on 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, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Once established, epialleles can be dominantly transmitted to naïve flies and induce paramutation. Importantly, epilines can be reset to a naïve state by disrupting chromatin interactions. Finally, we show that environmental changes can modulate the expressivity of the epialleles and we extend our paradigm to naturally occurring phenotypes. Our work sheds light on how nuclear organization and Polycomb group proteins contribute to epigenetically inheritable phenotypic variability.