Repression of myelin proteolipid protein gene expression is mediated through both general and cell type-specific negative regulatory elements in nonexpressing cells.
Repression of myelin proteolipid protein gene expression is mediated through both general and cell type-specific negative regulatory elements in nonexpressing cells.
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髓磷脂蛋白脂质蛋白基因表达的抑制是通过非表达细胞中的一般负调节元件和细胞类型特异性负调节元件介导的。
DOI：
10.1046/j.1471-4159.2002.00962.x
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发表时间：
2002
影响因子：
4.7
通讯作者：
Wight,PatriciaA
中科院分区：
文献类型：
--
作者：
Li,Shenyang;Dobretsova,Anna;Kokorina,NataliaA;Wight,PatriciaA
髓鞘蛋白脂质蛋白基因（Plp）主要在少突胶质细胞中表达。然而，该基因如何在非表达细胞中保持被抑制还没有被确定，如果抑制机制受损，可能会对生物体产生不利影响。以前的研究表明，第一个内含子含有元件，抑制在非表达细胞中的表达，尽管这些元件在8 kb内含子内的身份没有被表征。 在这里，我们报告了在非表达细胞（+/+ Li）中抑制Plp基因表达的多个负调控元件的定位。 这些元件（区域）中的两个对应于表达Plp的细胞（N20.1）所使用的那些，而另一个以细胞类型特异性方式起作用（即在+/+ Li肝细胞中起作用，但不在N20.1细胞中起作用）。 通过凝胶位移和DNA酶I足迹分析，与细胞类型特异性负调控区结合的因子似乎在+/+ Li细胞中比在N20.1细胞中丰富得多。 因此，Plp基因抑制是通过“一般”和细胞类型特异性负调控元件的组合作用介导的。此外，+/+ Li细胞中的阻遏不能通过抗沉默子/增强子元件克服，该元件先前已显示在N20.1细胞中起作用。
The myelin proteolipid protein gene (Plp) is expressed primarily in oligodendrocytes. Yet how the gene remains repressed in nonexpressing cells has not been defined, and potentially could cause adverse effects in an organism if the mechanism for repression was impaired. Previous studies suggest that the first intron contains element(s), which suppress expression in nonexpressing cells, although the identity of these elements within the 8 kb intron was not characterized. Here we report the localization of multiple negative regulatory elements that repressPlpgene expression in nonexpressing cells (+/+ Li). Two of these elements (regions) correspond to those used byPlpexpressing cells (N20.1), whilst another acts in a cell type‐specific manner (i.e. operational in +/+ Li liver cells, but not N20.1 cells). By gel‐shift and DNase I footprinting analyses, the factor(s) that bind to the cell type‐specific negative regulatory region appear to be far more abundant in +/+ Li cells than in N20.1 cells. Thus,Plpgene repression is mediated through the combinatorial action of both ‘general’ and cell type‐specific negative regulatory elements. Additionally, repression in +/+ Li cells cannot be overcome via an antisilencer/enhancer element, which previously has been shown to function in N20.1 cells.