Henikoff S
Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Bioessays. 1998 Jul;20(7):532-5. doi: 10.1002/(SICI)1521-1878(199807)20:7<532::AID-BIES3>3.0.CO;2-M.
Transgenic experiments in vertebrates often involve the insertion of tandem multiple-copy arrays at single sites. For many transgenes, expression is unpredictable from site to site, a phenomenon usually attributed to a repressive environment caused by nearby sequences. However, an alternative explanation comes from evidence that transgene repeat arrays in flies condense into heterochromatin, suggesting that low levels of expression in vertebrate transgene arrays might result from interactions between repeats within the array. A recent experiment using transgenic mouse lines demonstrates that reduction in copy number of silenced transgenes within an array leads to a striking increase in expression, demonstrating that silencing is intrinsic to the array, and is not attributable to position effects of nearby sequences. This work calls into question functions that have been attributed to vertebrate locus control regions and boundaries, and draws attention to the notion that repeat-induced gene silencing is a system for protection of eukaryotic genomes against threatening sequence elements.
脊椎动物中的转基因实验通常涉及在单个位点插入串联多拷贝阵列。对于许多转基因而言，不同位点的表达情况不可预测，这种现象通常归因于附近序列造成的抑制环境。然而，另一种解释来自于这样的证据：果蝇中的转基因重复阵列会浓缩成异染色质，这表明脊椎动物转基因阵列中低水平的表达可能是由阵列内重复序列之间的相互作用导致的。最近一项使用转基因小鼠品系的实验表明，阵列中沉默转基因拷贝数的减少会导致表达显著增加，这表明沉默是阵列固有的，并非归因于附近序列的位置效应。这项工作对赋予脊椎动物基因座控制区和边界的功能提出了质疑，并使人们注意到重复序列诱导的基因沉默是一种保护真核生物基因组免受威胁序列元件影响的系统这一观点。
