Milton N G, Bessis A, Changeux J P, Latchman D S
Department of Molecular Pathology, University College London Medical School, UK.
J Biol Chem. 1995 Jun 23;270(25):15143-7. doi: 10.1074/jbc.270.25.15143.
The regulatory region of the neuronal nicotinic acetylcholine receptor alpha 2 subunit gene, which contains six copies of the octamer-related sequence CCCCATGCAAT, is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This effect is in contrast to the previously documented inhibitory effect of Brn-3b on octamer-containing promoters that are activated by Brn-3a and Brn-3c. Activation of the alpha 2 gene by Brn-3b requires that both the POU domain and other N-terminal sequences are derived from Brn-3b and is dependent on the intactness of the alpha 2 gene regulatory region, being lost in truncated derivatives containing one, two, or four copies of the octamer-related sequence. Surprisingly, however, these truncated derivatives are activated by Brn-3c. These effects are discussed in terms of both the influence of the target sequence and its context in the promoter on activation by the various forms of Brn-3 as well as of the processes that restrict expression of the alpha 2 subunit gene to a few cells in the nervous system.
神经元烟碱型乙酰胆碱受体α2亚基基因的调控区域包含六个八聚体相关序列CCCCATGCAAT的拷贝,该区域可被Brn-3b POU家族转录因子激活,但不能被密切相关的因子Brn-3a和Brn-3c激活。这种效应与之前记录的Brn-3b对由Brn-3a和Brn-3c激活的含八聚体启动子的抑制作用相反。Brn-3b对α2基因的激活要求POU结构域和其他N端序列均来自Brn-3b,并且依赖于α2基因调控区域的完整性,在含有一个、两个或四个八聚体相关序列拷贝的截短衍生物中这种激活作用会丧失。然而,令人惊讶的是,这些截短衍生物可被Brn-3c激活。本文从靶序列及其在启动子中的背景对各种形式的Brn-3激活的影响以及将α2亚基基因表达限制在神经系统少数细胞中的过程这两方面对这些效应进行了讨论。