Mechanisms of heavy metal-dependent transactivation by transcription factor MTF-1

锌是一种必需的微量营养素。严格控制细胞内锌浓度是至关重要的。在哺乳动物中，金属硫蛋白(MT)是一种小的金属结合蛋白，在锌的动态平衡中起着重要作用。小鼠MT-I基因转录受金属反应元件结合转录因子-1(MTF-1)的调控，MTF-1被锌招募到启动子。我们检测了与增强转录激活相关的MT-I启动子染色质结构的变化。染色质免疫沉淀分析和MT-I启动子对微球菌核酸酶的敏感性表明，锌诱导的核小体去除可能会局部破坏启动子中的染色质结构。MT-I启动子上的核小体结构的快速破坏是由锌响应的活性MTF-1共激活复合体的募集所介导的。

Zinc is an essential micronutrient. It is critically important to control intracellular zinc concentrations tightly. In mammals, metallothionein (MT), a small metal-binding protein, plays important roles in zinc homeostasis. Mouse MT-I gene transcription is regulated by metal response element-binding transcription factor-1 (MTF-1), which is recruited to the promoter by zinc. We examined alterations in the chromatin structure of the MT-I promoter associated with enhanced transcriptional activation. Here, chromatin immunoprecipitation assays and micrococcal nuclease sensitivity of the MT-I promoter demonstrated that the chromatin structure in the promoter may be locally disrupted by zinc-induced nucleosome removal. Rapid disruption of nucleosome structure at the MT-I promoter is mediated by zinc-responsive recruitment of an active MTF-1-coactivator complex.