Stam M, Viterbo A, Mol J N, Kooter J M
Department of Molecular Genetics, Institute for Molecular Biological Sciences, BioCentrum Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
Mol Cell Biol. 1998 Nov;18(11):6165-77. doi: 10.1128/MCB.18.11.6165.
Posttranscriptional silencing of chalcone synthase (Chs) genes in petunia transformants occurs by introducing T-DNAs that contain a promoter-driven or promoterless Chs transgene. With the constructs we used, silencing occurs only by T-DNA loci which are composed of two or more T-DNA copies that are arranged as inverted repeats (IRs). Since we are interested in the mechanism by which these IR loci induce silencing, we have analyzed different IR loci and nonsilencing single-copy (S) T-DNA loci with respect to the expression and methylation of the transgenes residing in these loci. We show that in an IR locus, the transgenes located proximal to the IR center are much more highly methylated than are the distal genes. A strong silencing locus composed of three inverted T-DNAs bearing promoterless Chs transgenes was methylated across the entire locus. The host Chs genes in untransformed plants were moderately methylated, and no change in methylation was detected when the genes were silenced. Run-on transcription assays showed that promoter-driven transgenes located proximal to the center of a particular IR are transcriptionally more repressed than are the distal genes of the same IR locus. Transcription of the promoterless Chs transgenes could not be detected. In the primary transformant, some of the IR loci were detected together with an unlinked S locus. We observed that the methylation and expression characteristics of the transgenes of these S loci were comparable to those of the partner IR loci, suggesting that there has been cross talk between the two types of loci. Despite the similar features, S loci are unable to induce silencing, indicating that the palindromic arrangement of the Chs transgenes in the IR loci is critical for silencing. Since transcriptionally silenced transgenes in IRs can trigger posttranscriptional silencing of the host genes, our data are most consistent with a model of silencing in which the transgenes physically interact with the homologous host gene(s). The interaction may alter epigenetic features other than methylation, thereby impairing the regular production of mRNA.
通过导入含有启动子驱动或无启动子查尔酮合酶(Chs)转基因的T-DNA,矮牵牛转化体中Chs基因会发生转录后沉默。使用我们构建的载体,沉默仅发生在由两个或更多个以反向重复(IR)形式排列的T-DNA拷贝组成的T-DNA位点。由于我们对这些IR位点诱导沉默的机制感兴趣,因此我们分析了不同的IR位点和非沉默单拷贝(S)T-DNA位点中这些位点内转基因的表达和甲基化情况。我们发现,在一个IR位点中,位于IR中心近端的转基因比远端基因甲基化程度高得多。一个由三个携带无启动子Chs转基因的反向T-DNA组成的强沉默位点在整个位点上都发生了甲基化。未转化植物中的宿主Chs基因甲基化程度适中,基因沉默时未检测到甲基化变化。连续转录分析表明,位于特定IR中心近端的启动子驱动转基因在转录上比同一IR位点的远端基因受到更强的抑制。未检测到无启动子Chs转基因的转录。在初级转化体中,一些IR位点与一个不连锁的S位点一起被检测到。我们观察到这些S位点转基因的甲基化和表达特征与配对的IR位点相当,这表明两种类型的位点之间存在相互作用。尽管有相似的特征,但S位点无法诱导沉默,这表明IR位点中Chs转基因的回文排列对沉默至关重要。由于IR中转录沉默的转基因可以触发宿主基因的转录后沉默,我们的数据与一种沉默模型最为一致,即转基因与同源宿主基因发生物理相互作用。这种相互作用可能会改变除甲基化以外的表观遗传特征,从而损害mRNA的正常产生。