Zinc-dependent regulation of gene expression

基因表达的锌依赖性调节

• 批准号: 8932013
• 负责人: Amanda Jane Bird
• 金额: $ 28.64万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8932013
• 关键词: Address; Affect; Affinity; Alzheimer' s Disease; Beryllium; Binding; Biochemical; Biological Models; C2H2 Zinc Finger; Cell Cycle; Cell Maintenance; Cell physiology; Cells; Child; Defect; Diabetes Mellitus; Diarrhea; Dietary Zinc; Disease; Dissection; Ensure; Eukaryotic Cell; Fission Yeast; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Goals; Growth; Health; Hereditary Disease; Homeostasis; Human; In Vitro; Infertility; Ion Transport; Ions; Iron; Knowledge; Lead; Life; Malaria; Malignant neoplasm of esophagus; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Mediating; Metabolism; Metals; Modeling; Molecular Genetics; Mutation; Nuclear; Pathway interactions; Play; Pneumonia; Property; Proteins; RNA Interference; Repression; Research; Risk; Role; Sepsis; Starvation; System; Testing; Toxic effect; Transcription Repressor/Corepressor; Work; Yeast Model System; Zinc; Zinc Fingers; Zinc deficiency; extracellular; in vivo; insight; iron deficiency; iron metabolism; loss of function; malignant breast neoplasm; malignant mouth neoplasm; metabolomics; mortality; novel; public health relevance; response; sensor; uptake

DESCRIPTION (provided by applicant): Zinc is a metal element that is essential for life, but is toxic when present in excess. Cells therefore rely on mechanisms to maintain a relatively constant intracellular level of zinc despite fluctuations in the extracellular medium. To ensure that zinc levels are maintained at an optimal level for cell metabolism, the expression of genes necessary for zinc transport or zinc storage is often dependent upon cellular zinc levels. Although such changes in gene expression are central to zinc homeostasis, the identity of the factors that sense intracellular zinc levels and mediate these changes is largely unknown. The long-term goal of our research is to understand how eukaryotic cells sense and regulate intracellular zinc levels. To identify proteins that sense zinc, we have taken advantage of the versatile genetics of Schizosaccharomyces pombe. Using this model system we have isolated a novel factor that is required for zinc-dependent regulation of gene expression. This factor, designated Loz1, contains a double C2H2-type zinc finger domain that is essential for zinc-dependent regulation of gene expression. This proposal describes a combined molecular, genetic and biochemical approach to determine how Loz1 is regulated by zinc. Specifically, we will address whether Loz1 directly senses zinc levels, and whether this requires the double C2H2-type zinc finger domain.

描述（由申请人提供）：锌是一种生命必需的金属元素，但过量存在会产生毒性。因此，细胞依靠机制来维持相对恒定的细胞内锌水平，尽管细胞外介质存在波动。为了确保锌水平维持在细胞代谢的最佳水平，锌转运或锌储存所需基因的表达通常取决于细胞锌水平。尽管基因表达的这种变化对于锌稳态至关重要，但感知细胞内锌水平并介导这些变化的因子的身份在很大程度上尚不清楚。我们研究的长期目标是了解真核细胞如何感知和调节细胞内锌水平。为了识别感应锌的蛋白质，我们利用了粟酒裂殖酵母的多功能遗传学。使用该模型系统，我们分离出了锌依赖性基因表达调节所需的新因子。该因子被命名为 Loz1，包含一个双 C2H2 型锌指结构域，对于锌依赖性基因表达调节至关重要。该提案描述了一种结合分子、遗传和生化的方法来确定 Loz1 如何受锌调节。具体来说，我们将解决 Loz1 是否直接感知锌水平，以及这是否需要双 C2H2 型锌指结构域。