Wilson's disease is an autosomal recessive disorder resulting from copper excess. Some patients with clinical Wilson's disease symptoms exhibit no or only heterozygous pathogenic variants in the coding region of the disease‐causing ATP7B gene. Therefore, the ATP7B promoter region is of special interest. Metal‐responsive elements (MREs) located in the ATP7B promoter are promising motifs in modulating the ATP7B expression. We studied protein interaction of MREe, MREc, and MREd by electrophoretic mobility shift assays and revealed specific interactions for all MREs. We further narrowed down the specific binding site. Proteins potentially binding to the three MREs were identified by MatInspector analyses. Metal regulatory transcription factor 1 (MTF1) could be validated to bind to MREe by electrophoretic mobility shift assays. ATP7B promoter‐driven reporter gene expression was significantly increased because of this interaction. MTF1 is a strong candidate in regulating the ATP7B expression through MREe binding.

中文翻译：

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MTF1 与 ATP7B 启动子内的金属响应元件 e 结合，是调节 ATP7B 表达的有力候选者


威尔逊氏病是一种由铜过量引起的常染色体隐性遗传疾病。一些具有临床威尔逊病症状的患者在致病 ATP7B 基因的编码区中没有或仅表现出杂合致病性变异。因此，ATP7B 启动子区域受到特别关注。位于 ATP7B 启动子中的金属响应元件 (MRE) 是调节 ATP7B 表达的有希望的基序。我们通过电泳迁移率变动分析研究了 MREe、MREc 和 MREd 的蛋白质相互作用，并揭示了所有 MRE 的特定相互作用。我们进一步缩小了特异性结合位点的范围。通过 MatInspector 分析鉴定了可能与三种 MRE 结合的蛋白质。通过电泳迁移率变动分析，可以验证金属调节转录因子 1 (MTF1) 与 MREe 的结合。由于这种相互作用，ATP7B 启动子驱动的报告基因表达显着增加。 MTF1 是通过 MREe 结合调节 ATP7B 表达的有力候选者。