Donaldson K M, Karpen G H
Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Genetics. 1997 Feb;145(2):325-37. doi: 10.1093/genetics/145.2.325.
Position effect variegation (PEV) is the clonal inactivation of euchromatic or heterochromatic genes that are abnormally positioned within a chromosome. PEV can be influenced by modifiers in trans, including single gene mutations and the total amount of heterochromatin present in the genome. Terminal deletions of a Drosophila minichromosome (Dp1187) dramatically increase PEV of a yellow+ body-color gene located in cis, even when the terminal break is > 100 kb distal to the yellow gene. Here we demonstrate that terminal deficiency-associated PEV can be suppressed by the presence of a second minichromosome, a novel phenomenon termed "trans-suppression." The chromosomal elements responsible for trans-suppression were investigated using a series of minichromosomes with molecularly characterized deletions and inversions. The data suggest that trans-suppression does not involve communication between transcriptional regulatory elements on the homologues, a type of transvection known to act at the yellow locus. Furthermore, trans-suppression is not accomplished by titration through the addition of extra centric heterochromatin, a general mechanism for PEV suppression. We demonstrate that trans-suppression is disrupted by significant changes in the structure of the suppressing minichromosome, including deletions of the yellow region and centric heterochromatin, and large inversions of the centric heterochromatin. We conclude that chromosome pairing plays an important role in trans-suppression and discuss the possibility that terminal deficiency-associated PEV and trans-suppression reflect changes in nuclear positioning of the chromosomes and the gene, and/or the activity and distribution of telomere-binding proteins.
位置效应斑驳（PEV）是指常染色质或异染色质基因在染色体内位置异常导致的克隆性失活。PEV可受到反式作用修饰因子的影响，包括单基因突变和基因组中异染色质的总量。果蝇小染色体（Dp1187）的末端缺失显著增加了顺式作用的黄色体色基因的PEV，即使末端断裂位于黄色基因远端>100 kb处。在此，我们证明第二个小染色体的存在可抑制末端缺失相关的PEV，这是一种被称为“反式抑制”的新现象。我们使用一系列具有分子特征性缺失和倒位的小染色体研究了负责反式抑制的染色体元件。数据表明，反式抑制不涉及同源物上转录调控元件之间的通讯，这种通讯是一种已知在黄色位点起作用的反式效应。此外，反式抑制不是通过添加额外的着丝粒异染色质进行滴定来实现的，这是一种抑制PEV的普遍机制。我们证明，反式抑制会因抑制性小染色体结构的显著变化而被破坏，这些变化包括黄色区域和着丝粒异染色质的缺失以及着丝粒异染色质的大倒位。我们得出结论，染色体配对在反式抑制中起重要作用，并讨论了末端缺失相关的PEV和反式抑制反映染色体和基因的核定位变化以及端粒结合蛋白的活性和分布变化的可能性。
