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首页> 外文期刊>Molecular and Cellular Biology >The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated.
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The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated.

机译：增强子活性和κ免疫球蛋白基因的低甲基化之间的耦合受到发展调节。

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Previous studies have indicated that immunoglobulin enhancers are essential for establishing transcriptional competence but not for maintaining the activity of constitutively transcribed genes. To understand the basis for this developmental shift away from dependence on enhancer function, we have investigated the relationship between transcriptional activity and methylation status of the immunoglobulin kappa light-chain genes (kappa genes) in mouse cell lines representing different stages of B-cell maturation. Using pre-B-cell lines in which the level of a critical kappa enhancer-binding factor, NF-kappa B, was controlled by the administration or withdrawal of lipopolysaccharide and plasmacytoma lines that either contain or lack this factor, we studied the properties of endogenous kappa genes and of transfected kappa genes which were stably integrated into the genomes of these cells. In the pre-B cells, the exogenous (originally unmethylated) kappa genes, as well as endogenous kappa genes, were fully methylated and persistently dependent on enhancer function, even after more than 30 generations in a transcriptionally active state. In plasmacytoma cells, the endogenous kappa genes were invariably hypomethylated, whereas exogenous kappa genes were hypomethylated only in cells that contain NF-kappa B and are thus permissive for kappa enhancer function. These results indicate that the linkage of hypomethylation to enhancer-dependent activation of kappa transcription occurs after the pre-B-cell stage of development. The change in methylation status, together with associated changes in chromatin structure, may suffice to eliminate or lessen the importance of the enhancer for the maintenance of the transcriptionally active state.
机译：先前的研究表明，免疫球蛋白增强剂对于建立转录能力至关重要，但对于维持组成型转录基因的活性却不是必需的。为了了解这种发展转变摆脱依赖增强子功能的基础，我们研究了代表B细胞成熟不同阶段的小鼠细胞系中免疫球蛋白κ轻链基因（κ基因）的转录活性与甲基化状态之间的关系。 。使用前B细胞系（其中关键的κ增强子结合因子NF-κB的水平受含或缺乏该因子的脂多糖和浆细胞瘤细胞系的给药或撤药控制），我们研究了内源性κ基因和转染的κ基因已稳定整合到这些细胞的基因组中。在前B细胞中，外源（最初未甲基化）的Kappa基因以及内源性Kappa基因都被完全甲基化，并且即使在转录活性状态下经过30多个世代后，它们仍持续依赖增强子功能。在浆细胞瘤细胞中，内源性κ基因总是被低甲基化，而外源性κ基因仅在含有NF-κB的细胞中被低甲基化，因此允许κ增强子功能。这些结果表明，低甲基化与κ依赖性转录的增强子依赖性激活的联系发生在前B细胞发育阶段之后。甲基化状态的变化以及染色质结构的相关变化，可能足以消除或减轻增强子对维持转录活性状态的重要性。

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