Regulation Of Erythroid Gene Expression

我们已经讨论了 DNA:RNA 三螺旋形成在基因表达调节中的可能作用，特别是在人类 β 珠蛋白基因座中。 对于可以形成这种结构的碱基的组合有严格的规则。 我们寻找遵守这些规则的基因座。 最重要的是，我们发现成人β珠蛋白初级转录本中的内含子序列可以与β珠蛋白基因座控制区（LCR）中的靶位点形成三螺旋，LCR是β珠蛋白基因的主要正复合调节元件。 我们发现，当包含野生型第二个β珠蛋白内含子的全长转录物过表达时，它通过与LCR中的位点结合并取代转录因子来下调珠蛋白基因的表达。相同但内含子三链体形成序列突变的转录物没有效果。这似乎是一个防止β珠蛋白基因过度表达的反馈系统。 我们在基因组的其他地方发现了这种调节的另一个例子，表明这可能是一种普遍的调节机制。 寻找体内特异性识别三螺旋结构的蛋白质的工作已经开始。

We have addressed the possible role of DNA:RNA triple helix formation in regulation of gene expression, particularly in the human beta globin gene locus. There are strict rules for the combinations of bases that can form such structures. We searched for loci that obeyed those rules. Most significantly we have found that an intronic sequence within the adult human beta globin primary transcript can form a triple helix with a target site in the beta globin locus control region (LCR), the major positive compound regulatory element of the beta globin genes. We show that when a full length transcript containing the wild type second beta globin intron is overexpressed it downregulates expression of globin genes by binding to a site in the LCR and displacing transcription factors. A transcript that is identical but with the intronic triplex forming sequence mutated has no effect. This appears to be a feedback system to prevent overexpression of the beta globin genes. We have found another example of this regulation elsewhere in the genome, suggesting that this may a general regulatory mechanism. Work has begun to search for proteins that specifically recognize triple helical structures in vivo.