Beyond the Nucleosome: Epigenetic Aspects of Position–Effect Variegation in Drosophila
Beyond the Nucleosome: Epigenetic Aspects of Position–Effect Variegation in Drosophila
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DOI：
10.1016/s0092-8674(00)81159-9
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发表时间：
1998-05
期刊：
影响因子：
64.5
通讯作者：
Barbara T. Wakimoto
中科院分区：
文献类型：
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作者：
Barbara T. Wakimoto
现在人们普遍认识到，基因表达的遗传性变化可以在不伴随DNA序列变化的情况下发生。1930年，HJ Muller发现了位置效应杂色（PEV），首次描述了具有潜在表观遗传基础的现象。穆勒描述了果蝇的白色+（w+）眼睛颜色基因的突变，这种突变导致了基因表达中细胞与细胞之间的显著差异。嵌合体表型是由染色体位置效应引起的，其中重排断点将w+基因从其正常常染色质位置置换并将其置于异染色质附近。一些重排导致成人眼中红色小平面的大斑块与大白色斑块相邻。这种模式的杂色表明，决定表达或抑制的w+基因是在组织发育的早期，并保持在一个亚稳态通过多次细胞divisies.PEV提供了一个模型系统，以调查的性质的印记，指定的转录状态的基因和影响其稳定性的过程。由于异染色质可以诱导许多，如果不是全部，常染色质基因在果蝇中的失活，PEV的研究更普遍地解决异染色质和常染色质之间的功能差异。这两个染色体结构域最初是根据细胞学特性定义的。异染色质在整个细胞周期中（包括间期）保持其深染、浓缩的外观，而常染色质在间期出现弥散。异染色质是真核生物染色体中几乎普遍存在的特征。虽然异染色质在酵母中细胞学上不可见，但在S.酿酒酵母和S. pombe（由Grunstein 1998 [本期Cell]审查）。
It is now widely recognized that heritable changes in gene expression can occur without accompanying changes in DNA sequence. The discovery of position–effect variegation (PEV) by HJ Muller in 1930 provided the first description of a phenomenon with an underlying epigenetic basis. Muller described mutations of the white+(w+) eye color gene of Drosophila that resulted in striking, cell-to-cell variations in gene expression. The mosaic phenotypes were caused by a chromosomal position effect in which a rearrangement breakpoint displaced the w+ gene from its normal euchromatic location and placed it in the vicinity of heterochromatin. Some rearrangements resulted in large patches of red facets adjacent to large white patches in the adult eye. This pattern of variegation suggested that a decision to express or repress the w+ gene was made early during tissue development and was maintained in a metastable state through multiple cell divisions.PEV provides a model system to investigate the nature of an imprint that specifies the transcriptional state of a gene and the processes that influence its stability. Since heterochromatin can induce the inactivation of many, if not all, euchromatic genes in Drosophila, studies of PEV more generally address the functional differences between heterochromatin and euchromatin. These two chromosomal domains were originally defined on the basis of cytological properties. Heterochromatin retains its deeply staining, condensed appearance throughout the cell cycle, including interphase, whereas euchromatin appears diffuse during interphase. Heterochromatin is a nearly ubiquitous feature of the eukaryotic chromosome. Although heterochromatin is not cytologically visible in yeast, gene silencing phenomena with features similar to heterochromatin-induced gene inactivation in Drosophila are observed in S. cerevisiae and S. pombe (reviewed by Grunstein 1998 [this issue of Cell).