Wallrath L L, Elgin S C
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
Genes Dev. 1995 May 15;9(10):1263-77. doi: 10.1101/gad.9.10.1263.
A euchromatic gene placed in the vicinity of heterochromatin by a chromosomal rearrangement generally exhibits position effect variegation (PEV), a clonally inherited pattern showing gene expression in some somatic cells but not in others. The mechanism responsible for this loss of gene expression is investigated here using fly lines carrying a P element containing the Drosophila melanogaster white and hsp26 genes. Following mobilization of the P element, a screen for variegation of white expression recovered inserts at pericentric, telomeric, and fourth chromosome regions. Previously identified suppressors of PEV suppressed white variegation of pericentric and fourth chromosome inserts but not telomeric inserts on the second and third chromosomes. This implies a difference in the mechanism for gene repression at telomeres. Heat shock-induced hsp26 expression was reduced from pericentric and fourth chromosome inserts but not from telomeric inserts. Chromatin structure analysis revealed that the variegating inserts showed a reduction in accessibility to restriction enzyme digestion in the hsp26 regulatory region in isolated nuclei. Micrococcal nuclease digests showed that pericentric inserts were packaged in a more regular nucleosome array than that observed for euchromatic inserts. These data suggest that altered chromatin packaging plays a role in PEV.
通过染色体重排置于异染色质附近的常染色质基因通常会表现出位置效应斑驳（PEV），这是一种克隆遗传模式，在一些体细胞中显示基因表达，而在其他体细胞中则不表达。本文使用携带含有黑腹果蝇白色和hsp26基因的P元件的果蝇品系，研究了导致这种基因表达丧失的机制。在P元件动员后，对白色表达斑驳进行筛选，在着丝粒、端粒和第四条染色体区域回收了插入片段。先前鉴定的PEV抑制因子抑制了着丝粒和第四条染色体插入片段的白色斑驳，但不抑制第二和第三条染色体上的端粒插入片段。这意味着端粒处基因抑制机制存在差异。热休克诱导的hsp26表达从着丝粒和第四条染色体插入片段中降低，但从端粒插入片段中未降低。染色质结构分析表明，斑驳插入片段在分离的细胞核中，hsp26调控区域对限制性酶切的可及性降低。微球菌核酸酶消化表明，着丝粒插入片段比常染色质插入片段包装在更规则的核小体阵列中。这些数据表明，染色质包装改变在PEV中起作用。
