Sabl J F, Henikoff S
Department of Zoology, University of Washington, Seattle 98195, USA.
Genetics. 1996 Feb;142(2):447-58. doi: 10.1093/genetics/142.2.447.
The classical phenomenon of position-effect variegation (PEV) is the mosaic expression that occurs when a chromosomal rearrangement moves a euchromatic gene near heterochromatin. A striking feature of this phenomenon is that genes far away from the junction with heterochromatin can be affected, as if the heterochromatic state "spreads." We have investigated classical PEV of a Drosophila brown transgene affected by a heterochromatic junction approximately 60 kb away. PEV was enhanced when the transgene was locally duplicated using P transposase. Successive rounds of P transposase mutagenesis and phenotypic selection produced a series of PEV alleles with differences in phenotype that depended on transgene copy number and orientation. As for other examples of classical PEV, nearby heterochromatin was required for gene silencing. Modifications of classical PEV by alterations at a single site are unexpected, and these observations contradict models for spreading that invoke propagation of heterochromatin along the chromosome. Rather, our results support a model in which local alterations affect the affinity of a gene region for nearby heterochromatin via homology-based pairing, suggesting an alternative explanation for this 65-year-old phenomenon.
位置效应斑驳（PEV）的经典现象是当染色体重排使常染色质基因靠近异染色质时出现的镶嵌表达。这一现象的一个显著特征是，远离与异染色质连接处的基因也会受到影响，就好像异染色质状态在“扩散”。我们研究了一个果蝇棕色转基因的经典PEV，该转基因受到约60 kb外的异染色质连接处的影响。当使用P转座酶对转基因进行局部复制时，PEV增强。连续几轮的P转座酶诱变和表型选择产生了一系列PEV等位基因，其表型差异取决于转基因的拷贝数和方向。与经典PEV的其他例子一样，基因沉默需要附近的异染色质。单个位点的改变对经典PEV的修饰是出乎意料的，这些观察结果与异染色质沿染色体传播的扩散模型相矛盾。相反，我们的结果支持一种模型，即局部改变通过基于同源性的配对影响基因区域对附近异染色质的亲和力，这为这一有65年历史的现象提供了另一种解释。
