金属硫蛋白(MT)是参与多种过程的金属结合蛋白,包括金属稳态和解毒,氧化应激反应和细胞增殖。这些基因的异常表达和沉默在许多疾病中很重要。MT基因的几个正调节因子,包括金属响应元件结合转录因子(MTF)-1和上游刺激因子(USF)-1,已经被鉴定并且诱导机制已经被充分描述。然而,MT基因的负调节因子仍有待阐明。本综述组以往的研讨曾经显示,造血掌握转录因子,PU.1,通过其表观遗传活性直接抑制MT基因的表达水平,MT的上调导致髓样分化的有效抑制。本综述集中于PU.1和该基因的其他一些负调节因子,包括PZ120,DNA甲基转移酶3a与Mbd3和Brg1复合物,CCAAT增强子结合蛋白α和Ku蛋白,并描述了通过这些转录因子对MT基因的抑制。
Metallothioneins (MTs) are metal-binding proteins involved in diverse processes, including metal homeostasis and detoxification, the oxidative stress response and cell proliferation. Aberrant expression and silencing of these genes are important in a number of diseases. Several positive regulators of MT genes, including metal-responsive element-binding transcription factor (MTF)-1 and upstream stimulatory factor (USF)-1, have been identified and mechanisms of induction have been well described. However, the negative regulators of MT genes remain to be elucidated. Previous studies from the group of the present
review have revealed that the hematopoietic master transcription factor, PU.1, directly represses the expression levels of MT genes through its epigenetic activities, and upregulation of MT results in the potent inhibition of myeloid differentiation. The present
review focuses on PU.1 and several other negative regulators of this gene, including PZ120, DNA methyltransferase 3a with Mbd3 and Brg1 complex, CCAAT enhancer binding protein α and Ku protein, and describes the suppression of the MT genes through these transcription factors.