Hogstrand Christer, Zheng Dongling, Feeney Graham, Cunningham Phil, Kille Peter
Nutritional Sciences Division, School of Biomedical and Health Sciences, King's College London, Franklin-Wilkins Building, London, UK.
Biochem Soc Trans. 2008 Dec;36(Pt 6):1252-7. doi: 10.1042/BST0361252.
There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn(2+), resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5' regulatory region of genes in response to zinc. Treatment of cultured zebrafish ZF4 cells with siRNA (small interfering RNA) to MTF1 changed the transcriptional response to zinc for over 1000 genes, as assessed using an oligonucleotide microarray. From this primary list of MTF1-dependent genes, we identified a relatively small cohort that showed a configuration of MREs in their 5' regulatory regions similar to known MTF1 targets. This group showed a remarkable dominance of nucleic acid-binding proteins and other proteins involved in embryological development, implicating MTF1 as a master regulator of gene expression during development.
锌作为生物系统中的信号物质，其多样作用正日益受到重视。锌信号由不稳定的Zn(2+)细胞内浓度变化引起，导致基因组和非基因组效应。基因组反应主要由MTF1（金属调节转录因子1）介导，MTF1在锌的作用下与基因5'调控区的MREs（金属反应元件）结合。使用寡核苷酸微阵列评估，用针对MTF1的小干扰RNA（siRNA）处理培养的斑马鱼ZF4细胞，改变了对1000多个基因的锌转录反应。从这个MTF1依赖性基因的初步列表中，我们鉴定出一个相对较小的群体，其5'调控区的MREs配置与已知的MTF1靶标相似。该群体显示出核酸结合蛋白和其他参与胚胎发育的蛋白的显著优势，这表明MTF1是发育过程中基因表达的主要调节因子。
