Nourbakhsh M, Hoffmann K, Hauser H
Genetics of Eukaryotes, GBF-Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany.
EMBO J. 1993 Feb;12(2):451-9. doi: 10.1002/j.1460-2075.1993.tb05677.x.
The human interferon-beta (IFN-beta) promoter contains several functional domains that contribute to its virus-inducible regulation. One of them, PRDII, and NF-kappa B-binding sequence, can function as a constitutively activating element. Due to the presence of a negative regulatory domain that mediates a constitutive repression the natural IFN-beta promoter is silent in the non-induced state. Within this domain we have delimited an 11 bp element that acts as a negative regulatory element (NRE) of PRDII. Although the NRE is physically overlapping with PRDII in the IFN-beta promoter, it acts as a position-independent silencer of PRDII. Virus infection, which leads to the transcriptional activation of the IFN-beta promoter, does not alter the negative activity of the NRE on an isolated PRDII. It is the cooperative effect of PRDI and PRDII that is able to overcome the NRE function after virus infection. By UV cross-linking analysis using uninduced and virus-induced nuclear extracts, we show that two factors with molecular masses of approximately 95 and 100 kDa bind to the NRE.
人β干扰素（IFN-β）启动子包含几个对其病毒诱导性调节有作用的功能结构域。其中之一，PRDII，即NF-κB结合序列，可作为组成型激活元件发挥作用。由于存在介导组成型抑制的负调节结构域，天然IFN-β启动子在未诱导状态下是沉默的。在该结构域内，我们界定了一个11 bp的元件，它作为PRDII的负调节元件（NRE）发挥作用。尽管NRE在IFN-β启动子中与PRDII在物理上重叠，但它作为PRDII的位置独立沉默子发挥作用。导致IFN-β启动子转录激活的病毒感染，不会改变NRE对分离的PRDII的负活性。正是PRDI和PRDII的协同作用能够在病毒感染后克服NRE的功能。通过使用未诱导和病毒诱导的核提取物进行紫外线交联分析，我们表明分子量约为95和100 kDa的两种因子与NRE结合。
