Bird Amanda J, Blankman Elizabeth, Stillman David J, Eide David J, Winge Dennis R
Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
EMBO J. 2004 Mar 10;23(5):1123-32. doi: 10.1038/sj.emboj.7600122. Epub 2004 Feb 19.
The zinc-responsive transcriptional activator Zap1 regulates the expression of both high- and low-affinity zinc uptake permeases encoded by the ZRT1 and ZRT2 genes. Zap1 mediates this response by binding to zinc-responsive elements (ZREs) located within the promoter regions of each gene. ZRT2 has a remarkably different expression profile in response to zinc compared to ZRT1. While ZRT1 is maximally induced during zinc limitation, ZRT2 is repressed in low zinc but remains induced upon zinc supplementation. In this study, we determined the mechanism underlying this paradoxical Zap1-dependent regulation of ZRT2. We demonstrate that a nonconsensus ZRE (ZRT2 ZRE3), which overlaps with one of the ZRT2 transcriptional start sites, is essential for repression of ZRT2 in low zinc and that Zap1 binds to ZRT2 ZRE3 with a low affinity. The low-affinity ZRE is also essential for the ZRT2 expression profile. These results indicate that the unusual pattern of ZRT2 regulation among Zap1 target genes involves the antagonistic effect of Zap1 binding to a low-affinity ZRE repressor site and high-affinity ZREs required for activation.
锌响应转录激活因子Zap1调控由ZRT1和ZRT2基因编码的高亲和力和低亲和力锌摄取通透酶的表达。Zap1通过与位于每个基因启动子区域内的锌响应元件（ZREs）结合来介导这种反应。与ZRT1相比，ZRT2对锌的反应具有明显不同的表达谱。虽然ZRT1在锌限制期间被最大程度地诱导，但ZRT2在低锌条件下被抑制，但在补充锌后仍被诱导。在本研究中，我们确定了这种矛盾的Zap1依赖性ZRT2调控的潜在机制。我们证明，一个与ZRT2转录起始位点之一重叠的非一致性ZRE（ZRT2 ZRE3）对于低锌条件下ZRT2的抑制至关重要，并且Zap1以低亲和力与ZRT2 ZRE3结合。低亲和力ZRE对于ZRT2的表达谱也至关重要。这些结果表明，Zap1靶基因中ZRT2调控的异常模式涉及Zap1与低亲和力ZRE阻遏位点结合以及激活所需的高亲和力ZREs的拮抗作用。
