Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP
Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP
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DOI：
10.1101/gad.1634608
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发表时间：
2008-02-15
影响因子：
10.5
通讯作者：
Misteli, Tom
中科院分区：
文献类型：
--
作者：
Takizawa, Takumi;Gudla, Prabhakar R.;Misteli, Tom
染色体和基因在哺乳动物细胞核内非随机排列。然而，核定位在基因表达中的功能意义尚不清楚。在这里，我们通过比较单等位基因表达基因的活性和非活性拷贝在单细胞核中的位置，直接探讨了核定位和基因活性之间的关系。我们证明星形胶质细胞特异性标记物 GFAP（胶质纤维酸性蛋白）在皮质星形胶质细胞中单等位表达。活性等位基因的选择以随机方式发生，并且通常通过细胞分裂来维持。利用 GFAP 的单等位基因表达，我们发现功能不同的等位基因在细胞核内占据不同的径向位置，并与核内区室有不同的关联。此外，不同染色体上协调调节的星形胶质细胞特异性基因在非活动状态下空间关联，并在激活时解离。这些结果为间期核内个体基因等位基因的功能相关差异定位提供了直接证据。
Chromosomes and genes are nonrandomly arranged within the mammalian cell nucleus. However, the functional significance of nuclear positioning in gene expression is unclear. Here we directly probed the relationship between nuclear positioning and gene activity by comparing the location of the active and inactive copies of a monoallelically expressed gene in single cell nuclei. We demonstrate that the astrocyte-specific marker GFAP (glial fibrillary acidic protein) is monoallelically expressed in cortical astrocytes. Selection of the active allele occurs in a stochastic manner and is generally maintained through cell division. Taking advantage of the monoallelic expression of GFAP, we show that the functionally distinct alleles occupy differential radial positions within the cell nucleus and differentially associate with intranuclear compartments. In addition, coordinately regulated astrocyte-specific genes on distinct chromosomes spatially associate in their inactive state and dissociate upon activation. These results provide direct evidence for function-related differential positioning of individual gene alleles within the interphase nucleus.