Nuclear pore association confers optimal expression levels for an inducible yeast gene
Nuclear pore association confers optimal expression levels for an inducible yeast gene
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DOI：
10.1038/nature04845
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发表时间：
2006-06-08
期刊：
影响因子：
64.8
通讯作者：
Gasser, Susan M.
中科院分区：
文献类型：
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作者：
Taddei, Angela;Van Houwe, Griet;Gasser, Susan M.
细胞核分成小室的组织创造了微环境，被认为促进了不同的核功能(1)。在出芽酵母中，沉默染色质区域，如端粒和交配型位点，聚集在核膜上，形成有利于基因抑制的区域（1,2）。其他报告表明，基因转录发生在核周围，显然是由于基因与核孔复合物的关联（3-5）。在这里，我们报道了一个亚端粒基因，HXK1（己糖激酶同工酶1），通过在非葡萄糖碳源上生长的转录激活导致其重新定位到核孔。这种重新定位需要30个非翻译区（UTR），这对于有效的信使RNA加工和输出至关重要，与相关报告一致(6)。然而，通过基于反激活子VP16的替代途径激活HXK1，使位点远离核外周，并取消了半乳糖对HXK1的正常诱导。值得注意的是，当我们通过拮抗或促进与孔的关联来干扰HXK1定位时，转录水平分别降低或提高。由此我们得出结论，核位置在决定最佳基因表达水平方面具有积极作用。
The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions(1). In budding yeast, regions of silent chromatin, such as those at telomeres and mating-type loci, cluster at the nuclear envelope creating zones that favour gene repression(1,2). Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes(3-5). Here we report that transcriptional activation of a subtelomeric gene, HXK1 ( hexokinase isoenzyme 1), by growth on a non-glucose carbon source led to its relocalization to nuclear pores. This relocation required the 30 untranslated region ( UTR), which is essential for efficient messenger RNA processing and export, consistent with an accompanying report(6). However, activation of HXK1 by an alternative pathway based on the transactivator VP16 moved the locus away from the nuclear periphery and abrogated the normal induction of HXK1 by galactose. Notably, when we interfered with HXK1 localization by either antagonizing or promoting association with the pore, transcript levels were reduced or enhanced, respectively. From this we conclude that nuclear position has an active role in determining optimal gene expression levels.