An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression.
An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression.
复制标题
转录的上游激活剂协调提高基因表达的水平和表观遗传稳定性。
DOI：
10.1073/pnas.93.24.13914
复制
发表时间：
1996
影响因子：
11.1
通讯作者：
Martin,DI
中科院分区：
文献类型：
--
作者：
Magis,W;Fiering,S;Groudine,M;Martin,DI
小鼠金属硫蛋白i （mMT-I）启动子被金属反应元件结合转录因子（MTF）激活，该因子在重金属刺激下结合金属反应元件（MREs）。我们分析了8个K562红白血病细胞克隆，每个克隆都携带一个mMT-I/β-geo构建体的单一整合拷贝，使用一个可以独立评估β-geo表达水平和沉默率的系统。在这些克隆中，基础表达量和沉默率随整合位点的不同而有很大的独立差异。这意味着转录率和沉默率是由转基因调控元件与整合位点的相互作用决定的独立特性。用锌诱导mMT-I启动子既能提高表达水平，又能强烈延缓β-geo表达的沉默。在给定的整合位点，表达水平和沉默受到诱导的协调影响。结合早期对远端金属响应元件的研究，这些结果表明，与启动子的距离可能决定一个因子是否能提高转录率。刺激MRE可以增加转录并克服染色质的抑制作用；我们认为这些功能是有联系的。
The mouse metallothionein-I (mMT-I) promoter is activated by the metal response element-binding transcription factor (MTF), which binds metal response elements (MREs) when stimulated with heavy metals. We analyzed eight K562 erythroleukemia cell clones, each carrying a single integrated copy of an mMT-I/β-geo construct, using a system that can independently assess the level of β-geo expression and the rate at which it is silenced. In these clones, basal expression and rate of silencing vary widely and independently with integration site. This implies that the rates of transcription and of silencing are separate properties determined by interaction of the regulatory elements of the transgene with the site of integration. Induction of the mMT-I promoter with zinc both increases expression level and strongly retards silencing of β-geo expression. At a given integration site, expression level and silencing are affected coordinately by induction. Taken together with earlier studies of distant metal-responsive elements, these results suggest that distance from the promoter may determine whether a factor can increase transcription rate. Stimulation of an MRE can both increase transcription and overcome repressive effects of chromatin; we suggest that these functions are linked.