Department of Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Mol Genet Genomics. 2012 Jul;287(7):591-606. doi: 10.1007/s00438-012-0702-z. Epub 2012 Jun 24.
Paramutation is an epigenetic process in which a combination of alleles in a heterozygous organism results in a meiotically stable change in expression of one of the alleles. The mechanisms underlying paramutation are being actively investigated, and examples have been described in both plants and mammals, suggesting that it may utilize epigenetic mechanisms that are widespread and evolutionarily conserved. Paramutation at the well-studied maize b1 locus requires a control region consisting of seven 853 bp tandem repeats. To study the conservation of the epigenetic mechanisms underlying seemingly unique epigenetic processes such as paramutation, we created transgenic Drosophila melanogaster carrying the maize b1 control region adjacent to the Drosophila white reporter gene. We show that the b1 tandem repeats cause silencing of the white reporter in Drosophila. A single copy of the tandem repeat sequence is sufficient to cause silencing, and silencing strength increases as the number of tandem repeats increases. Additionally, transgenic lines with the full seven tandem repeats demonstrate evidence of either pairing-sensitive silencing and silencing in trans, or epigenetic activation in trans. These trans-interactions are dependent on repeat number, similar to maize b1 paramutation. Also, as in maize, the tandem repeats are bidirectionally transcribed in Drosophila. These results indicate that the maize b1 tandem repeats function as an epigenetic silencer and mediate trans-interactions in Drosophila, and support the hypothesis that the mechanisms underlying such epigenetic processes are conserved.
等位基因转变是一种表观遗传过程，在杂合子生物中，等位基因的组合导致其中一个等位基因的表达发生有丝分裂稳定的变化。等位基因转变的机制正在积极研究中，在植物和哺乳动物中都有描述，这表明它可能利用了广泛存在且在进化上保守的表观遗传机制。在研究得很好的玉米 b1 基因座上的等位基因转变需要一个由七个 853bp 串联重复组成的控制区。为了研究似乎独特的表观遗传过程（如等位基因转变）背后的表观遗传机制的保守性，我们创建了携带玉米 b1 控制区的转基因果蝇，该控制区紧邻果蝇的白色报告基因。我们发现 b1 串联重复会导致果蝇中白色报告基因的沉默。单个串联重复序列足以引起沉默，并且随着串联重复数量的增加，沉默强度增加。此外，具有完整七个串联重复的转基因系显示出配对敏感沉默和反式沉默，或反式表观遗传激活的证据。这些反式相互作用依赖于重复数，类似于玉米 b1 等位基因转变。同样，与玉米一样，串联重复在果蝇中双向转录。这些结果表明，玉米 b1 串联重复作为一种表观遗传沉默子在果蝇中发挥作用，并介导反式相互作用，支持这样的表观遗传过程的机制是保守的假设。
