The vagaries of variegating transgenes

The vagaries of variegating transgenes
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DOI:
10.1002/bies.950181111
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发表时间:
1996-01-01
期刊:
影响因子:
4
通讯作者:
Whitelaw, Emma
Whitelaw, Emma
中科院分区:
生物学3区
文献类型:
--
作者:
Martin, David I. K.;Whitelaw, Emma

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转基因在小鼠中的表达,当用可以区分单个细胞的测定法检查时,通常发现是异细胞的或杂色的。转基因表达的株系间差异可能主要是由于其表达的细胞比例的差异。由着丝粒异染色质引起的杂色沉默已被很好地描述,但其他因素也可能影响小鼠中的转基因沉默。转基因的串联阵列本身形成异染色质,并且一些细胞谱系可能倾向于沉默转基因,因为它们的细胞核中存在广泛的兼性异染色质。转基因内的转录调控元件抑制沉默,染色质蛋白的株系特异性差异可能强烈影响杂色的程度。小鼠中多种分化细胞谱系的可及性表明,它们可能提供了一种工具,用于剖析染色质介导的沉默在细胞分化和组织特异性基因表达中的作用。
Expression of transgenes in mice, when examined with assays that can distinguish individual cells, is often found to be heterocellular, or variegated. Line‐to‐line variations in expression of a transgene may be due largely to differences in the proportion of cells in which it is expressed. Variegated silencing by centromeric heterochromatin is well described, but other factors may also affect transgene silencing in mice. Tandem arrays of transgenes themselves form heterochromatin, and some cell lineages may tend to silence transgenes because of extensive facultative heterochromatin in their nuclei. Thecis‐acting transcriptional control elements within a transgene inhibit silencing, and strainspecific differences in chromatin proteins may strongly influence the extent of variegation. The accessibility of multiple differentiated cell lineages in mice suggests that they may provide a tool for dissecting the role of chromatin‐mediated silencing in cell differentiation and tissue‐specific gene expression.