Taddei Angela, Van Houwe Griet, Hediger Florence, Kalck Veronique, Cubizolles Fabien, Schober Heiko, Gasser Susan M
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Nature. 2006 Jun 8;441(7094):774-8. doi: 10.1038/nature04845.
The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions. 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. Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes. 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 3' untranslated region (UTR), which is essential for efficient messenger RNA processing and export, consistent with an accompanying report. 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.
细胞核组织成亚区室会形成微环境，人们认为这些微环境有助于实现不同的核功能。在出芽酵母中，沉默染色质区域，如端粒和交配型位点处的区域，聚集在核膜处，形成有利于基因抑制的区域。其他报告表明基因转录发生在核周边，显然是由于基因与核孔复合体的关联。我们在此报告，在非葡萄糖碳源上生长时，端粒旁基因HXK1（己糖激酶同工酶1）的转录激活导致其重新定位到核孔。这种重新定位需要3'非翻译区（UTR），该区域对于有效的信使RNA加工和输出至关重要，这与一篇伴随报告一致。然而，基于反式激活因子VP16的另一条途径对HXK1的激活使该基因座远离核周边，并消除了半乳糖对HXK1的正常诱导。值得注意的是，当我们通过拮抗或促进与核孔的结合来干扰HXK1的定位时，转录水平分别降低或升高。由此我们得出结论，核位置在确定最佳基因表达水平方面具有积极作用。
