Brown Jill M, Green Joanne, das Neves Ricardo Pires, Wallace Helen A C, Smith Andrew J H, Hughes Jim, Gray Nicki, Taylor Steve, Wood William G, Higgs Douglas R, Iborra Francisco J, Buckle Veronica J
Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, England, UK.
J Cell Biol. 2008 Sep 22;182(6):1083-97. doi: 10.1083/jcb.200803174.
Genes on different chromosomes can be spatially associated in the nucleus in several transcriptional and regulatory situations; however, the functional significance of such associations remains unclear. Using human erythropoiesis as a model, we show that five cotranscribed genes, which are found on four different chromosomes, associate with each other at significant but variable frequencies. Those genes most frequently in association lie in decondensed stretches of chromatin. By replacing the mouse alpha-globin gene cluster in situ with its human counterpart, we demonstrate a direct effect of the regional chromatin environment on the frequency of association, whereas nascent transcription from the human alpha-globin gene appears unaffected. We see no evidence that cotranscribed erythroid genes associate at shared transcription foci, but we do see stochastic clustering of active genes around common nuclear SC35-enriched speckles (hence the apparent nonrandom association between genes). Thus, association between active genes may result from their location on decondensed chromatin that enables clustering around common nuclear speckles.
在几种转录和调控情况下，位于不同染色体上的基因可在细胞核内发生空间关联；然而，这种关联的功能意义仍不清楚。以人类红细胞生成作为模型，我们发现位于四条不同染色体上的五个共转录基因以显著但可变的频率相互关联。那些最常发生关联的基因位于染色质的解凝聚区域。通过将小鼠α-珠蛋白基因簇原位替换为人类对应基因簇，我们证明了区域染色质环境对关联频率有直接影响，而人类α-珠蛋白基因的新生转录似乎未受影响。我们没有发现共转录的红系基因在共享转录位点发生关联的证据，但我们确实看到活性基因围绕常见的富含核SC35的斑点随机聚集（因此基因之间存在明显的非随机关联）。因此，活性基因之间的关联可能是由于它们位于解凝聚的染色质上，从而能够围绕常见的核斑点聚集。
