Haussecker Dirk, Proudfoot Nicholas J
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
Mol Cell Biol. 2005 Nov;25(21):9724-33. doi: 10.1128/MCB.25.21.9724-9733.2005.
The widespread occurrence of intergenic transcription in eukaryotes is increasingly evident. Intergenic transcription in the beta-globin gene cluster has been described in murine and human cells, and models for a role in gene and chromatin activation have been proposed. In this study, we analyze intergenic transcription and the chromatin state throughout the human beta-globin gene cluster and find that the data are not consistent with such activation-linked models. Thus, intergenic transcript levels correlate with neither chromatin activation nor globin gene expression. Instead, we find that intergenic transcripts of the beta-globin gene cluster are specifically upregulated in Dicer-deficient cells. This is accompanied by a shift towards more activated chromatin as indicated by changes in histone tail modifications. Our results strongly implicate RNA interference (RNAi)-related mechanisms in regulating intergenic transcription in the human beta-globin gene cluster and further suggest that RNAi-dependent chromatin silencing in vertebrates is not restricted to the centromeres.
真核生物中基因间转录的广泛存在日益明显。β-珠蛋白基因簇中的基因间转录已在小鼠和人类细胞中被描述，并且有人提出了其在基因和染色质激活中发挥作用的模型。在本研究中，我们分析了整个人类β-珠蛋白基因簇中的基因间转录和染色质状态，发现数据与这种激活相关模型不一致。因此，基因间转录水平既与染色质激活无关，也与珠蛋白基因表达无关。相反，我们发现β-珠蛋白基因簇的基因间转录本在Dicer缺陷细胞中特异性上调。这伴随着组蛋白尾部修饰变化所表明的向更活跃染色质的转变。我们的结果有力地表明RNA干扰（RNAi）相关机制在调节人类β-珠蛋白基因簇中的基因间转录，并且进一步表明脊椎动物中依赖RNAi的染色质沉默并不局限于着丝粒。
