Shopland Lindsay S, Johnson Carol V, Byron Meg, McNeil John, Lawrence Jeanne B
Department of Cell Biology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
J Cell Biol. 2003 Sep 15;162(6):981-90. doi: 10.1083/jcb.200303131.
Typically, eukaryotic nuclei contain 10-30 prominent domains (referred to here as SC-35 domains) that are concentrated in mRNA metabolic factors. Here, we show that multiple specific genes cluster around a common SC-35 domain, which contains multiple mRNAs. Nonsyntenic genes are capable of associating with a common domain, but domain "choice" appears random, even for two coordinately expressed genes. Active genes widely separated on different chromosome arms associate with the same domain frequently, assorting randomly into the 3-4 subregions of the chromosome periphery that contact a domain. Most importantly, visualization of six individual chromosome bands showed that large genomic segments ( approximately 5 Mb) have striking differences in organization relative to domains. Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not. All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences. Similarly, late-replicating DNA generally avoids SC-35 domains. These findings suggest a functional rationale for gene clustering in chromosomal bands, which relates to nuclear clustering of genes with SC-35 domains. Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic "neighborhoods."
通常，真核细胞核含有10 - 30个显著的结构域（此处称为SC - 35结构域），这些结构域集中了mRNA代谢因子。在此，我们表明多个特定基因聚集在一个共同的SC - 35结构域周围，该结构域包含多个mRNA。非同源基因能够与一个共同的结构域相关联，但结构域“选择”似乎是随机的，即使对于两个协同表达的基因也是如此。在不同染色体臂上广泛分离的活跃基因经常与同一个结构域相关联，随机分布在与一个结构域接触的染色体周边的3 - 4个亚区域中。最重要的是，对六个单独染色体带的观察表明，大的基因组片段（约5 Mb）相对于结构域在组织上有显著差异。某些带显示出广泛的接触，常常与一个SC - 35结构域对齐或环绕该结构域，而其他带则不然。所有三个富含基因的反向带比缺乏基因的吉姆萨暗带更明显地表现出这种情况，形态计量分析显示出统计学上的显著差异。同样，晚复制的DNA通常避开SC - 35结构域。这些发现提示了染色体带中基因聚类的功能原理，这与基因与SC - 35结构域的核内聚类有关。我们提出，SC - 35结构域不是剪接因子的随机储存库，也不是单个高度活跃基因上积累的因子，而是众多聚类基因的功能中心，形成局部常染色质“邻域”。
