Plant K E, Routledge S J, Proudfoot N J
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Mol Cell Biol. 2001 Oct;21(19):6507-14. doi: 10.1128/MCB.21.19.6507-6514.2001.
Our previous studies on nascent transcription across the human beta-globin gene cluster revealed the presence of intergenic transcripts in addition to the expected genic transcripts. We now show that transcription into the beta-globin locus control region (LCR) begins within an ERV9 endogenous retroviral long terminal repeat upstream of DNase I hypersensitive site 5. However, in a transgenic mouse, which has the human beta-globin LCR but lacks the ERV9 LTR, transcription begins upstream of the transgenic locus. We postulate that in this transgenic mouse nearby endogenous mouse promoters are activated by the LCR. Intergenic transcription is also detected across the whole transgenic globin gene locus independently of the stage of erythroid development. Intergenic transcription in the beta-globin cluster is erythroid specific; however, it can be induced in nonerythroid cells by several means: by transinduction with a plasmid transcribing part of the cluster, by exogenous addition of transcription factors, and by treatment with the histone deacetylase inhibitor trichostatin A.
我们之前对人类β-珠蛋白基因簇新生转录的研究表明，除了预期的基因转录本外，还存在基因间转录本。我们现在发现，向β-珠蛋白基因座控制区（LCR）的转录始于脱氧核糖核酸酶I超敏位点5上游的一个ERV9内源性逆转录病毒长末端重复序列内。然而，在一只具有人类β-珠蛋白LCR但缺乏ERV9 LTR的转基因小鼠中，转录始于转基因基因座的上游。我们推测，在这只转基因小鼠中，附近的内源性小鼠启动子被LCR激活。在整个转基因珠蛋白基因座中也检测到了基因间转录，且与红系发育阶段无关。β-珠蛋白基因簇中的基因间转录是红系特异性的；然而，它可以通过几种方式在非红系细胞中诱导产生：通过用转录该基因簇一部分的质粒进行反式诱导、通过外源添加转录因子以及通过用组蛋白脱乙酰酶抑制剂曲古抑菌素A处理。
