Zhou Guo-Ling, Xin Li, Song Wei, Di Li-Jun, Liu Guang, Wu Xue-Song, Liu De-Pei, Liang Chih-Chuan
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
Mol Cell Biol. 2006 Jul;26(13):5096-105. doi: 10.1128/MCB.02454-05.
RNA polymerases can be shared by a particular group of genes in a transcription "factory" in nuclei, where transcription may be coordinated in concert with the distribution of coexpressed genes in higher-eukaryote genomes. Moreover, gene expression can be modulated by regulatory elements working over a long distance. Here, we compared the conformation of a 130-kb chromatin region containing the mouse alpha-globin cluster and their flanking housekeeping genes in 14.5-day-postcoitum fetal liver and brain cells. The analysis of chromatin conformation showed that the active alpha1 and alpha2 globin genes and upstream regulatory elements are in close spatial proximity, indicating that looping may function in the transcriptional regulation of the mouse alpha-globin cluster. In fetal liver cells, the active alpha1 and alpha2 genes, but not the inactive zeta gene, colocalize with neighboring housekeeping genes C16orf33, C16orf8, MPG, and C16orf35. This is in sharp contrast with the mouse alpha-globin genes in nonexpressing cells, which are separated from the congregated housekeeping genes. A comparison of RNA polymerase II (Pol II) occupancies showed that active alpha1 and alpha2 gene promoters have a much higher RNA Pol II enrichment in liver than in brain. The RNA Pol II occupancy at the zeta gene promoter, which is specifically repressed during development, is much lower than that at the alpha1 and alpha2 promoters. Thus, the mouse alpha-globin gene cluster may be regulated through moving in or out active globin gene promoters and regulatory elements of a preexisting transcription factory in the nucleus, which is maintained by the flanking clustered housekeeping genes, to activate or inactivate alpha-globin gene expression.
RNA聚合酶可由细胞核中转录“工厂”内特定的一组基因共享，在该转录“工厂”中，转录可能与高等真核生物基因组中共表达基因的分布协同进行。此外，基因表达可由远距离起作用的调控元件进行调节。在此，我们比较了在妊娠14.5天的胎肝和脑细胞中，包含小鼠α-珠蛋白基因簇及其侧翼管家基因的130kb染色质区域的构象。染色质构象分析表明，活跃的α1和α2珠蛋白基因以及上游调控元件在空间上紧密相邻，这表明环化可能在小鼠α-珠蛋白基因簇的转录调控中发挥作用。在胎肝细胞中，活跃的α1和α2基因，而非不活跃的ζ基因，与相邻的管家基因C16orf33、C16orf8、MPG和C16orf35共定位。这与非表达细胞中的小鼠α-珠蛋白基因形成鲜明对比，后者与聚集的管家基因分离。RNA聚合酶II（Pol II）占有率的比较表明，活跃的α1和α2基因启动子在肝脏中的RNA Pol II富集程度远高于在大脑中的富集程度。在发育过程中被特异性抑制的ζ基因启动子处的RNA Pol II占有率远低于α1和α2启动子处的占有率。因此，小鼠α-珠蛋白基因簇可能通过细胞核中预先存在的转录工厂的活跃珠蛋白基因启动子和调控元件的移入或移出进行调控，该转录工厂由侧翼成簇的管家基因维持，以激活或失活α-珠蛋白基因表达。
