Zink Daniele, Amaral Margarida D, Englmann Andreas, Lang Susanne, Clarke Luka A, Rudolph Carsten, Alt Felix, Luther Kathrin, Braz Carla, Sadoni Nicolas, Rosenecker Joseph, Schindelhauer Dirk
Ludwig Maximilians University Munich, Department of Biology II, 80336 Munich, Germany.
J Cell Biol. 2004 Sep 13;166(6):815-25. doi: 10.1083/jcb.200404107.
We investigated in different human cell types nuclear positioning and transcriptional regulation of the functionally unrelated genes GASZ, CFTR, and CORTBP2, mapping to adjacent loci on human chromosome 7q31. When inactive, GASZ, CFTR, and CORTBP2 preferentially associated with the nuclear periphery and with perinuclear heterochromatin, whereas in their actively transcribed states the gene loci preferentially associated with euchromatin in the nuclear interior. Adjacent genes associated simultaneously with these distinct chromatin fractions localizing at different nuclear regions, in accordance with their individual transcriptional regulation. Although the nuclear localization of CFTR changed after altering its transcription levels, the transcriptional status of CFTR was not changed by driving this gene into a different nuclear environment. This implied that the transcriptional activity affected the nuclear positioning, and not vice versa. Together, the results show that small chromosomal subregions can display highly flexible nuclear organizations that are regulated at the level of individual genes in a transcription-dependent manner.
我们在不同人类细胞类型中研究了功能不相关的基因GASZ、CFTR和CORTBP2的核定位及转录调控，这些基因定位于人类7号染色体7q31的相邻位点。当处于非活性状态时，GASZ、CFTR和CORTBP2优先与核周边及核周异染色质相关联，而在它们的活跃转录状态下，基因位点优先与核内常染色质相关联。相邻基因根据其各自的转录调控，同时与定位于不同核区域的这些不同染色质组分相关联。尽管改变CFTR的转录水平后其核定位发生了变化，但将该基因置于不同的核环境中并未改变CFTR的转录状态。这表明转录活性影响核定位，而非相反。总之，结果表明小的染色体亚区域可呈现高度灵活的核组织，其在单个基因水平上以转录依赖的方式受到调控。
