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Interchromosomal contacts between regulatory regions trigger stable transgenerational epigenetic inheritance in Drosophila
Molecular Cell ( IF 14.5 ) Pub Date : 2024-12-11 , DOI: 10.1016/j.molcel.2024.11.021
Maximilian H. Fitz-James, Gonzalo Sabarís, Peter Sarkies, Frédéric Bantignies, Giacomo Cavalli

Non-genetic information can be inherited across generations in a process known as transgenerational epigenetic inheritance (TEI). In Drosophila, hemizygosity of the Fab-7 regulatory element triggers inheritance of the histone mark H3K27me3 at a homologous locus on another chromosome, resulting in heritable epigenetic differences in eye color. Here, by mutating transcription factor binding sites within the Fab-7 element, we demonstrate the importance of the proteins pleiohomeotic and GAGA factor in the establishment and maintenance of TEI. We show that these proteins function by recruiting the polycomb repressive complex 2 and by mediating interchromosomal chromatin contacts between Fab-7 and its homologous locus, respectively. Using an in vivo synthetic biology system to induce them, we then show that chromatin contacts alone can establish TEI, providing a mechanism by which hemizygosity of one locus can establish epigenetic memory at another distant locus in trans through chromatin contacts.

中文翻译:


调节区域之间的染色体间接触触发果蝇稳定的跨代表观遗传



非遗传信息可以在称为跨代表观遗传 (TEI) 的过程中代代遗传。在果蝇中,Fab-7 调节元件的半合子性触发组蛋白标记 H3K27me3 在另一条染色体上的同源基因座的遗传,导致眼睛颜色的可遗传表观遗传差异。在这里,通过突变 Fab-7 元件内的转录因子结合位点,我们证明了多效同源和 GAGA 因子在建立和维持 TEI 中的重要性。我们表明,这些蛋白质分别通过募集多梳抑制复合物 2 和介导 Fab-7 与其同源基因座之间的染色体间染色质接触来发挥作用。 使用体内合成生物学系统诱导它们,然后我们表明仅染色质接触就可以建立 TEI,提供了一种机制,通过该机制,一个基因座的半合子可以通过染色质接触在另一个遥远的基因座建立表观遗传记忆。
更新日期:2024-12-11
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